Variant 1-1284021-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001130413.4(SCNN1D):c.395C>T(p.Pro132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,432,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 21)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

SCNN1D
NM_001130413.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0043523908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1D	NM_001130413.4 link	c.395C>T	p.Pro132Leu	missense_variant	5/18	ENST00000379116.10	NP_001123885.2	P51172-3
SCNN1D	NR_037668.3 link	n.621C>T		non_coding_transcript_exon_variant	5/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1D	ENST00000379116.10 link	c.395C>T	p.Pro132Leu	missense_variant	5/18	5	NM_001130413.4	ENSP00000368411.5		P51172-3

Frequencies

GnomAD3 genomes

AF:

0.000635

AC:

AN:

126062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000182

Gnomad OTH

AF:

0.000602

GnomAD3 exomes

AF:

0.000172

AC:

AN:

98622

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

55866

show subpopulations

Gnomad AFR exome

AF:

0.00223

Gnomad AMR exome

AF:

0.000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000268

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000464

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000149

AC:

195

AN:

1306166

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

642744

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.000405

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000711

Gnomad4 SAS exome

AF:

0.000188

Gnomad4 FIN exome

AF:

0.0000644

Gnomad4 NFE exome

AF:

0.0000923

Gnomad4 OTH exome

AF:

0.000224

GnomAD4 genome

AF:

0.000634

AC:

AN:

126160

Hom.:

Cov.:

AF XY:

0.000681

AC XY:

AN XY:

60214

show subpopulations

Gnomad4 AFR

AF:

0.00211

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000124

Gnomad4 NFE

AF:

0.000182

Gnomad4 OTH

AF:

0.000595

Alfa

AF:

0.000246

Hom.:

Bravo

AF:

0.000831

ExAC

AF:

0.000141

AC:

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

May 28, 2024

The c.395C>T (p.P132L) alteration is located in exon 5 (coding exon 5) of the SCNN1D gene. This alteration results from a C to T substitution at nucleotide position 395, causing the proline (P) at amino acid position 132 to be replaced by a leucine (L). 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

0.090

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.3

DANN

Benign

0.77

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.054

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.071

MVP

0.10

ClinPred

0.022

GERP RS

-1.9

Varity_R

0.058

gMVP

0.054

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