Variant 1-1281497-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001130413.4(SCNN1D):c.164C>T(p.Ala55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,531,100 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 9 hom. )

Consequence

SCNN1D
NM_001130413.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.10

Variant links:

Genes affected

SCNN1D (HGNC:10601): (sodium channel epithelial 1 subunit delta) Predicted to enable ligand-gated sodium channel activity. Predicted to be involved in sodium ion transmembrane transport. Located in actin cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SCNN1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036496222).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1D	NM_001130413.4 link	c.164C>T	p.Ala55Val	missense_variant	Exon 3 of 18	ENST00000379116.10	NP_001123885.2	P51172-3
SCNN1D	NR_037668.3 link	n.390C>T		non_coding_transcript_exon_variant	Exon 3 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCNN1D	ENST00000379116.10 link	c.164C>T	p.Ala55Val	missense_variant	Exon 3 of 18	5	NM_001130413.4	ENSP00000368411.5	P51172-3
SCNN1D	ENST00000379101.8 link	n.164C>T		non_coding_transcript_exon_variant	Exon 3 of 17	1		ENSP00000449804.1	F8VWH5
SCNN1D	ENST00000338555 link	c.-235C>T		5_prime_UTR_variant	Exon 1 of 15	2		ENSP00000339504.2	P51172-1
SCNN1D	ENST00000400928 link	c.-235C>T		5_prime_UTR_variant	Exon 2 of 16	5		ENSP00000383717.3	P51172-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000440

AC:

AN:

129502

Hom.:

AF XY:

0.000426

AC XY:

AN XY:

70412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000251

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00335

Gnomad SAS exome

AF:

0.000370

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000597

Gnomad OTH exome

AF:

0.00126

GnomAD4 exome

AF:

0.000202

AC:

278

AN:

1378804

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

132

AN XY:

680072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00188

Gnomad4 SAS exome

AF:

0.000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.000295

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00329

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000422

Hom.:

Bravo

AF:

0.000310

ExAC

AF:

0.000199

AC:

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.164C>T (p.A55V) alteration is located in exon 3 (coding exon 3) of the SCNN1D gene. This alteration results from a C to T substitution at nucleotide position 164, causing the alanine (A) at amino acid position 55 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.3

DANN

Benign

0.37

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.18

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.057

MutPred

0.11

Loss of catalytic residue at A55 (P = 0.1391);

MVP

0.11

ClinPred

0.0098

GERP RS

-3.4

Varity_R

0.047

gMVP

0.015

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