dbSNP rs764040424: SCNN1D:p.Gly149Arg (chr1-1284071-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001130413.4(SCNN1D):c.445G>A(p.Gly149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G149W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., cov: 8)

Exomes 𝑓: 0.000012 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

SCNN1D
NM_001130413.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.137

Publications

2 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034455687).

BP6

Variant 1-1284071-G-A is Benign according to our data. Variant chr1-1284071-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3793288.Status of the report is criteria_provided_single_submitter, 1 stars.

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.445G>A	p.Gly149Arg	missense	Exon 5 of 18	NP_001123885.2	P51172-3
	SCNN1D	NR_037668.3		n.671G>A		non_coding_transcript_exon	Exon 5 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCNN1D	ENST00000379116.10	TSL:5 MANE Select	c.445G>A	p.Gly149Arg	missense	Exon 5 of 18	ENSP00000368411.5	P51172-3
SCNN1D	ENST00000325425.12	TSL:1	c.151G>A	p.Gly51Arg	missense	Exon 2 of 15	ENSP00000321594.8	P51172-2
SCNN1D	ENST00000379101.8	TSL:1	n.445G>A		non_coding_transcript_exon	Exon 5 of 17	ENSP00000449804.1	F8VWH5

Frequencies

GnomAD3 genomes

AF:

0.0000184

AC:

AN:

54204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000348

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000455

AC:

AN:

65882

AF XY:

0.0000523

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:

0.0000344

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1138756

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

556064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21914

American (AMR)

AF:

0.00

AC:

AN:

10408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17238

East Asian (EAS)

AF:

0.00

AC:

AN:

21952

South Asian (SAS)

AF:

0.000102

AC:

AN:

49164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4494

European-Non Finnish (NFE)

AF:

0.00000965

AC:

AN:

932318

Other (OTH)

AF:

0.00

AC:

AN:

44048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000184

AC:

AN:

54204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

25320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10996

American (AMR)

AF:

0.00

AC:

AN:

5470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1630

East Asian (EAS)

AF:

0.00

AC:

AN:

1886

South Asian (SAS)

AF:

0.00

AC:

AN:

1360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

156

European-Non Finnish (NFE)

AF:

0.0000348

AC:

AN:

28704

Other (OTH)

AF:

0.00

AC:

AN:

698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000675

Hom.:

ExAC

AF:

0.0000188

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.067

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

2.9

(source)

DANN

Benign

0.89

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.34

M_CAP

Benign

0.011

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.90

PhyloP100

0.14

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.14

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Benign

0.40

Vest4

0.10

MutPred

0.15

Gain of MoRF binding (P = 0.0092)

MVP

0.12

ClinPred

0.051

GERP RS

-0.88

Varity_R

0.12

gMVP

0.096

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over