1-1284071-G-T

Position:

• chr1-1284071-G-T

Variant summary

Our verdict is Likely benign. Variant got -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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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

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

Verdict is Likely_benign. Variant got -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCNN1D	NM_001130413.4	c.445G>T	p.Gly149Trp	missense_variant	5/18	ENST00000379116.10	NP_001123885.2
SCNN1D	NR_037668.3	n.671G>T		non_coding_transcript_exon_variant	5/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1D	ENST00000379116.10	c.445G>T	p.Gly149Trp	missense_variant	5/18	5	NM_001130413.4	ENSP00000368411.5

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

Gnomad4 AFR exome AF: 0.000319

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000965

Gnomad4 OTH exome AF: 0.0000454

GnomAD4 genome Cov.: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2021

The c.445G>T (p.G149W) alteration is located in exon 5 (coding exon 5) of the SCNN1D gene. This alteration results from a G to T substitution at nucleotide position 445, causing the glycine (G) at amino acid position 149 to be replaced by a tryptophan (W). 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	0.084
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;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.87	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.015	D;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

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

Other links and lift over

dbSNP: rs764040424; hg19: chr1-1219451;