12-50059116-T-C

Variant names:

• chr12-50059116-T-C
• NM_001095.4:c.350T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001095.4(ASIC1):​c.350T>C​(p.Leu117Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC1	NM_001095.4	c.350T>C	p.Leu117Pro	missense_variant	Exon 2 of 12	ENST00000447966.7	NP_001086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC1	ENST00000447966.7	c.350T>C	p.Leu117Pro	missense_variant	Exon 2 of 12	1	NM_001095.4	ENSP00000400228.3
ASIC1	ENST00000228468.8	c.350T>C	p.Leu117Pro	missense_variant	Exon 2 of 12	1		ENSP00000228468.4
ASIC1	ENST00000550558.5	n.350T>C		non_coding_transcript_exon_variant	Exon 2 of 13	2		ENSP00000448263.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.350T>C (p.L117P) alteration is located in exon 2 (coding exon 1) of the ASIC1 gene. This alteration results from a T to C substitution at nucleotide position 350, causing the leucine (L) at amino acid position 117 to be replaced by a proline (P). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.079	B;D
Vest4		0.91
MutPred		0.71		Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);
MVP		0.94
MPC		1.5
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.93
gMVP		1.0

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: chr12-50452899;