rs1158764009

Variant names:

• chr1-1281252-C-A
• rs1158764009
• NM_001130413.4:c.32C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-1281252-C-A
• chr1-1281252-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130413.4(SCNN1D):​c.32C>A​(p.Pro11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000094 in 1,383,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: SCNN1D NM_001130413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.28

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059827566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1D	NM_001130413.4	c.32C>A	p.Pro11Gln	missense_variant	Exon 2 of 18	ENST00000379116.10	NP_001123885.2
SCNN1D	NR_037668.3	n.258C>A		non_coding_transcript_exon_variant	Exon 2 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1D	ENST00000379116.10	c.32C>A	p.Pro11Gln	missense_variant	Exon 2 of 18	5	NM_001130413.4	ENSP00000368411.5
SCNN1D	ENST00000379101.8	n.32C>A		non_coding_transcript_exon_variant	Exon 2 of 17	1		ENSP00000449804.1
SCNN1D	ENST00000338555	c.-480C>A		5_prime_UTR_variant	Exon 1 of 15	2		ENSP00000339504.2
SCNN1D	ENST00000400928	c.-367C>A		5_prime_UTR_variant	Exon 1 of 16	5		ENSP00000383717.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000149 AC: 2 AN: 134496 Hom.: 0 AF XY: 0.0000137 AC XY: 1 AN XY: 73252

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000241

GnomAD4 exome AF: 0.00000940 AC: 13 AN: 1383414 Hom.: 0 Cov.: 32 AF XY: 0.00000879 AC XY: 6 AN XY: 682610

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0040
DANN	Benign	0.44
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.17
MutPred		0.15		Loss of glycosylation at P11 (P = 0.0225);
MVP		0.085
ClinPred		0.026	T
GERP RS		-1.6
Varity_R		0.037
gMVP		0.024

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1158764009; hg19: chr1-1216632;