16-23189488-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001039.4(SCNN1G):c.435C>T(p.Ser145Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 1,614,156 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 69 hom. )

Consequence

SCNN1G
NM_001039.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.799

Publications

10 publications found

Variant links:

Genes affected

SCNN1G (HGNC:10602): (sodium channel epithelial 1 subunit gamma) Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the gamma subunit, and mutations in this gene have been associated with Liddle syndrome. [provided by RefSeq, Apr 2009]

SCNN1G Gene-Disease associations (from GenCC):

Liddle syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
bronchiectasis with or without elevated sweat chloride 3
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
Liddle syndrome 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
pseudohypoaldosteronism, type IB1, autosomal recessive
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

SCNN1G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 16-23189488-C-T is Benign according to our data. Variant chr16-23189488-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 318347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.799 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.435C>T	p.Ser145Ser	synonymous_variant	Exon 3 of 13	ENST00000300061.3	NP_001030.2	P51170A5X2V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3 link	c.435C>T	p.Ser145Ser	synonymous_variant	Exon 3 of 13	1	NM_001039.4	ENSP00000300061.2		P51170

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

1046

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00864

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00660

AC:

1660

AN:

251470

AF XY:

0.00668

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.00226

Gnomad NFE exome

AF:

0.00859

Gnomad OTH exome

AF:

0.00814

GnomAD4 exome

AF:

0.00760

AC:

11110

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

5560

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00702

AC:

235

AN:

33480

American (AMR)

AF:

0.00420

AC:

188

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26136

East Asian (EAS)

AF:

0.000554

AC:

AN:

39700

South Asian (SAS)

AF:

0.00978

AC:

844

AN:

86256

European-Finnish (FIN)

AF:

0.00258

AC:

138

AN:

53420

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00814

AC:

9052

AN:

1111996

Other (OTH)

AF:

0.00878

AC:

530

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

637

1274

1910

2547

3184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

344

688

1032

1376

1720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00690

AC:

1051

AN:

152280

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

467

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00758

AC:

315

AN:

41564

American (AMR)

AF:

0.00327

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5170

South Asian (SAS)

AF:

0.00953

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00864

AC:

588

AN:

68024

Other (OTH)

AF:

0.00805

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

112

167

223

279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00779

Hom.:

Bravo

AF:

0.00698

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.0101

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SCNN1G: BP4, BP7, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 11, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Sep 17, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ser145Ser in exon 3 of SCNN1G: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.9% (38/4394) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs62639702). -

Bronchiectasis with or without elevated sweat chloride 3;C4748251:Liddle syndrome 2;C5774176:Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

Jul 26, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Liddle syndrome 2

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

(source)

DANN

Benign

0.52

PhyloP100

-0.80

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over