Variant 16-23189602-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001039.4(SCNN1G):c.549C>T(p.Gly183Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 1,613,944 control chromosomes in the GnomAD database, including 4,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 384 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3634 hom. )

Consequence

SCNN1G
NM_001039.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.04

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-23189602-C-T is Benign according to our data. Variant chr16-23189602-C-T is described in ClinVar as [Benign]. Clinvar id is 165174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23189602-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1G	NM_001039.4 linkuse as main transcript	c.549C>T	p.Gly183Gly	synonymous_variant	3/13	ENST00000300061.3	NP_001030.2	P51170A5X2V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3 linkuse as main transcript	c.549C>T	p.Gly183Gly	synonymous_variant	3/13	1	NM_001039.4	ENSP00000300061.2		P51170

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9882

AN:

152130

Hom.:

380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0518

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.0185

Gnomad SAS

AF:

0.0385

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0739

Gnomad OTH

AF:

0.0616

GnomAD3 exomes

AF:

0.0612

AC:

15397

AN:

251492

Hom.:

609

AF XY:

0.0613

AC XY:

8337

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.0352

Gnomad ASJ exome

AF:

0.0638

Gnomad EAS exome

AF:

0.0175

Gnomad SAS exome

AF:

0.0331

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.0732

Gnomad OTH exome

AF:

0.0668

GnomAD4 exome

AF:

0.0670

AC:

97911

AN:

1461696

Hom.:

3634

Cov.:

AF XY:

0.0662

AC XY:

48146

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0503

Gnomad4 AMR exome

AF:

0.0366

Gnomad4 ASJ exome

AF:

0.0620

Gnomad4 EAS exome

AF:

0.0151

Gnomad4 SAS exome

AF:

0.0340

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.0704

Gnomad4 OTH exome

AF:

0.0671

GnomAD4 genome

AF:

0.0651

AC:

9906

AN:

152248

Hom.:

384

Cov.:

AF XY:

0.0663

AC XY:

4938

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0523

Gnomad4 AMR

AF:

0.0506

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.0188

Gnomad4 SAS

AF:

0.0381

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.0739

Gnomad4 OTH

AF:

0.0614

Alfa

AF:

0.0684

Hom.:

247

Bravo

AF:

0.0591

Asia WGS

AF:

0.0620

AC:

214

AN:

3478

EpiCase

AF:

0.0641

EpiControl

AF:

0.0715

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 15, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 03, 2020	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Gly183Gly 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 6.9% (596/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5737). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.082

DANN

Benign

0.50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over