1-1284071-G-T

Variant names:

• chr1-1284071-G-T
• rs764040424
• NM_001130413.4:c.445G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001130413.4(SCNN1D):​c.445G>T​(p.Gly149Trp) 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G149R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SCNN1D NM_001130413.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.137
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.061598748).

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>T	p.Gly149Trp	missense	Exon 5 of 18	NP_001123885.2	P51172-3
	SCNN1D	NR_037668.3		n.671G>T		non_coding_transcript_exon	Exon 5 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1D	ENST00000379116.10	TSL:5 MANE Select	c.445G>T	p.Gly149Trp	missense	Exon 5 of 18	ENSP00000368411.5	P51172-3
	SCNN1D	ENST00000325425.12	TSL:1	c.151G>T	p.Gly51Trp	missense	Exon 2 of 15	ENSP00000321594.8	P51172-2
	SCNN1D	ENST00000379101.8	TSL:1	n.445G>T		non_coding_transcript_exon	Exon 5 of 17	ENSP00000449804.1	F8VWH5

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome AF: 0.0000167 AC: 19 AN: 1138756 Hom.: 0 Cov.: 19 AF XY: 0.0000198 AC XY: 11 AN XY: 556064

African (AFR) AF: 0.000319 AC: 7 AN: 21914

American (AMR) AF: 0.00 AC: 0 AN: 10408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17238

East Asian (EAS) AF: 0.00 AC: 0 AN: 21952

South Asian (SAS) AF: 0.00 AC: 0 AN: 49164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37220

Middle Eastern (MID) AF: 0.000223 AC: 1 AN: 4494

European-Non Finnish (NFE) AF: 0.00000965 AC: 9 AN: 932318

Other (OTH) AF: 0.0000454 AC: 2 AN: 44048

GnomAD4 genome Cov.: 8

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.91
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.87	T
PhyloP100		0.14
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.015	D
Vest4		0.26
MutPred		0.27		Gain of MoRF binding (P = 0.0373)
MVP		0.11
ClinPred		0.32	T
GERP RS		-0.88
Varity_R		0.082
gMVP		0.10
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs764040424; hg19: chr1-1219451;