dbSNP rs748234253: SCNN1D:p.Thr191Met (chr1-1285939-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001130413.4(SCNN1D):c.572C>T(p.Thr191Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,549,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SCNN1D
NM_001130413.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.845

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046989232).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130413.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1D	NM_001130413.4	MANE Select	c.572C>T	p.Thr191Met	missense	Exon 7 of 18	NP_001123885.2	P51172-3
	SCNN1D	NR_037668.3		n.704C>T		non_coding_transcript_exon	Exon 6 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCNN1D	ENST00000379116.10	TSL:5 MANE Select	c.572C>T	p.Thr191Met	missense	Exon 7 of 18	ENSP00000368411.5	P51172-3
SCNN1D	ENST00000325425.12	TSL:1	c.278C>T	p.Thr93Met	missense	Exon 4 of 15	ENSP00000321594.8	P51172-2
SCNN1D	ENST00000379101.8	TSL:1	n.478C>T		non_coding_transcript_exon	Exon 6 of 17	ENSP00000449804.1	F8VWH5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000369

AC:

AN:

162672

AF XY:

0.0000564

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000469

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1396866

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

688272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31974

American (AMR)

AF:

0.00

AC:

AN:

40610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23946

East Asian (EAS)

AF:

0.0000271

AC:

AN:

36936

South Asian (SAS)

AF:

0.0000507

AC:

AN:

78838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.0000186

AC:

AN:

1077468

Other (OTH)

AF:

0.00

AC:

AN:

57610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000171

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.52

M_CAP

Benign

0.0046

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.34

PhyloP100

-0.84

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.15

REVEL

Benign

0.093

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Vest4

0.21

MVP

0.18

ClinPred

0.45

GERP RS

-0.80

Varity_R

0.042

gMVP

0.14

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over