1-1281490-G-T

Variant names:

• chr1-1281490-G-T
• rs552813227
• NM_001130413.4:c.157G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130413.4(SCNN1D):​c.157G>T​(p.Gly53Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. G53R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCNN1D NM_001130413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08741194).

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.157G>T	p.Gly53Trp	missense	Exon 3 of 18	NP_001123885.2
	SCNN1D	NR_037668.3		n.383G>T		non_coding_transcript_exon	Exon 3 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1D	ENST00000379116.10	TSL:5 MANE Select	c.157G>T	p.Gly53Trp	missense	Exon 3 of 18	ENSP00000368411.5
	SCNN1D	ENST00000379101.8	TSL:1	n.157G>T		non_coding_transcript_exon	Exon 3 of 17	ENSP00000449804.1
	SCNN1D	ENST00000338555.6	TSL:2	c.-242G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000339504.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.2
DANN	Benign	0.42
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.48
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.22
MutPred		0.25		Gain of glycosylation at P50 (P = 0.0651)
MVP		0.099
ClinPred		0.072	T
GERP RS		-3.4
PromoterAI		-0.055	Neutral
Varity_R		0.065
gMVP		0.12
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: rs552813227; hg19: chr1-1216870;