16-23189488-C-T

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

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

Conservation

PhyloP100: -0.799
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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
SCNN1GNM_001039.4 linkc.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
SCNN1GENST00000300061.3 linkc.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.:
8
Cov.:
32
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
GnomAD3 exomes
AF:
0.00660
AC:
1660
AN:
251470
Hom.:
9
AF XY:
0.00668
AC XY:
908
AN XY:
135912
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 SAS exome
AF:
0.00918
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.:
69
Cov.:
43
AF XY:
0.00765
AC XY:
5560
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00702
Gnomad4 AMR exome
AF:
0.00420
Gnomad4 ASJ exome
AF:
0.00103
Gnomad4 EAS exome
AF:
0.000554
Gnomad4 SAS exome
AF:
0.00978
Gnomad4 FIN exome
AF:
0.00258
Gnomad4 NFE exome
AF:
0.00814
Gnomad4 OTH exome
AF:
0.00878
GnomAD4 genome
AF:
0.00690
AC:
1051
AN:
152280
Hom.:
8
Cov.:
32
AF XY:
0.00627
AC XY:
467
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00758
Gnomad4 AMR
AF:
0.00327
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00953
Gnomad4 FIN
AF:
0.00189
Gnomad4 NFE
AF:
0.00864
Gnomad4 OTH
AF:
0.00805
Alfa
AF:
0.00779
Hom.:
2
Bravo
AF:
0.00698
Asia WGS
AF:
0.0180
AC:
64
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
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Sep 17, 2018
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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 -

Jun 11, 2021
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Jan 13, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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
DANN
Benign
0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62639702; hg19: chr16-23200809; COSMIC: COSV55599290; API