rs5734

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001039.4(SCNN1G):c.387T>C(p.Tyr129Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,870 control chromosomes in the GnomAD database, including 76,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6188 hom., cov: 32)

Exomes 𝑓: 0.31 ( 70206 hom. )

Consequence

SCNN1G
NM_001039.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.39

Publications

22 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-23189440-T-C is Benign according to our data. Variant chr16-23189440-T-C is described in ClinVar as Benign. ClinVar VariationId is 165172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4 link	c.387T>C	p.Tyr129Tyr	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.387T>C	p.Tyr129Tyr	synonymous_variant	Exon 3 of 13	1	NM_001039.4	ENSP00000300061.2		P51170

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41404

AN:

152000

Hom.:

6165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.276

GnomAD2 exomes

AF:

0.309

AC:

77645

AN:

251300

AF XY:

0.305

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.436

Gnomad ASJ exome

AF:

0.305

Gnomad EAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.306

AC:

447170

AN:

1461752

Hom.:

70206

Cov.:

AF XY:

0.305

AC XY:

221919

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.148

AC:

4948

AN:

33478

American (AMR)

AF:

0.431

AC:

19282

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

8016

AN:

26136

East Asian (EAS)

AF:

0.162

AC:

6422

AN:

39700

South Asian (SAS)

AF:

0.271

AC:

23379

AN:

86256

European-Finnish (FIN)

AF:

0.369

AC:

19678

AN:

53392

Middle Eastern (MID)

AF:

0.273

AC:

1567

AN:

5744

European-Non Finnish (NFE)

AF:

0.311

AC:

345510

AN:

1111932

Other (OTH)

AF:

0.304

AC:

18368

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

19310

38619

57929

77238

96548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11200

22400

33600

44800

56000

<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:

0.273

AC:

41478

AN:

152118

Hom.:

6188

Cov.:

AF XY:

0.274

AC XY:

20398

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.158

AC:

6551

AN:

41530

American (AMR)

AF:

0.356

AC:

5446

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1023

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

927

AN:

5156

South Asian (SAS)

AF:

0.268

AC:

1290

AN:

4808

European-Finnish (FIN)

AF:

0.362

AC:

3824

AN:

10578

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21462

AN:

67980

Other (OTH)

AF:

0.275

AC:

580

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1491

2982

4472

5963

7454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.309

Hom.:

4919

Bravo

AF:

0.269

Asia WGS

AF:

0.274

AC:

950

AN:

3478

EpiCase

AF:

0.306

EpiControl

AF:

0.307

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 24, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Tyr129Tyr 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 32.1% (2759/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5734). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

Jan 13, 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. -

Liddle syndrome 2

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.036

(source)

DANN

Benign

0.26

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(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