dbSNP rs201680784: SCNN1D:p.Pro132Leu (chr1-1284021-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 16/21 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

Publications

4 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 -4 ACMG points.

BP4

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

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.395C>T	p.Pro132Leu	missense	Exon 5 of 18	NP_001123885.2	P51172-3
	SCNN1D	NR_037668.3		n.621C>T		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.395C>T	p.Pro132Leu	missense	Exon 5 of 18	ENSP00000368411.5	P51172-3
SCNN1D	ENST00000325425.12	TSL:1	c.101C>T	p.Pro34Leu	missense	Exon 2 of 15	ENSP00000321594.8	P51172-2
SCNN1D	ENST00000379101.8	TSL:1	n.395C>T		non_coding_transcript_exon	Exon 5 of 17	ENSP00000449804.1	F8VWH5

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

GnomAD2 exomes

AF:

0.000172

AC:

AN:

98622

AF XY:

0.000143

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 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

African (AFR)

AF:

0.00239

AC:

AN:

25944

American (AMR)

AF:

0.000405

AC:

AN:

19748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22462

East Asian (EAS)

AF:

0.0000711

AC:

AN:

28140

South Asian (SAS)

AF:

0.000188

AC:

AN:

63986

European-Finnish (FIN)

AF:

0.0000644

AC:

AN:

46552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5416

European-Non Finnish (NFE)

AF:

0.0000923

AC:

AN:

1040274

Other (OTH)

AF:

0.000224

AC:

AN:

53644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.000634

AC:

AN:

126160

Hom.:

Cov.:

AF XY:

0.000681

AC XY:

AN XY:

60214

show subpopulations

African (AFR)

AF:

0.00211

AC:

AN:

31766

American (AMR)

AF:

0.00

AC:

AN:

12088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3176

East Asian (EAS)

AF:

0.00

AC:

AN:

4256

South Asian (SAS)

AF:

0.00

AC:

AN:

3510

European-Finnish (FIN)

AF:

0.000124

AC:

AN:

8088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.000182

AC:

AN:

60548

Other (OTH)

AF:

0.000595

AC:

AN:

1682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.000374

Hom.:

Bravo

AF:

0.000831

ExAC

AF:

0.000141

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

0.090

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.3

(source)

DANN

Benign

0.77

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.33

M_CAP

Benign

0.033

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

PhyloP100

-1.3

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.13

REVEL

Benign

0.054

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.071

MVP

0.10

ClinPred

0.022

GERP RS

-1.9

Varity_R

0.058

gMVP

0.054

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over