12-50058779-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001095.4(ASIC1):​c.13G>T​(p.Ala5Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ASIC1
NM_001095.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33
Variant links:
Genes affected
ASIC1 (HGNC:100): (acid sensing ion channel subunit 1) This gene encodes a member of the acid-sensing ion channel (ASIC) family of proteins, which are part of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. Members of the ASIC family are sensitive to amiloride and function in neurotransmission. The encoded proteins function in learning, pain transduction, touch sensation, and development of memory and fear. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

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ACMG classification

Classification made for transcript

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=0.05317411).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASIC1NM_001095.4 linkc.13G>T p.Ala5Ser missense_variant Exon 2 of 12 ENST00000447966.7 NP_001086.2 P78348-2A8K1U5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASIC1ENST00000447966.7 linkc.13G>T p.Ala5Ser missense_variant Exon 2 of 12 1 NM_001095.4 ENSP00000400228.3 P78348-2
ASIC1ENST00000228468.8 linkc.13G>T p.Ala5Ser missense_variant Exon 2 of 12 1 ENSP00000228468.4 P78348-1
ASIC1ENST00000550558.5 linkn.13G>T non_coding_transcript_exon_variant Exon 2 of 13 2 ENSP00000448263.1 F8VSK4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.13G>T (p.A5S) alteration is located in exon 2 (coding exon 1) of the ASIC1 gene. This alteration results from a G to T substitution at nucleotide position 13, causing the alanine (A) at amino acid position 5 to be replaced by a serine (S). 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
0.086
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.15
.;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.27
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.16
N;N
REVEL
Benign
0.16
Sift
Benign
0.55
T;T
Sift4G
Benign
0.71
T;T
Polyphen
0.0080
B;B
Vest4
0.25
MutPred
0.17
Gain of phosphorylation at A5 (P = 0.0145);Gain of phosphorylation at A5 (P = 0.0145);
MVP
0.18
MPC
0.80
ClinPred
0.15
T
GERP RS
2.9
Varity_R
0.044
gMVP
0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50452562; API