12-50059070-C-G

Variant names:

• chr12-50059070-C-G
• NM_001095.4:c.304C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001095.4(ASIC1):​c.304C>G​(p.Gln102Glu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASIC1 NM_001095.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26314285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC1	NM_001095.4	c.304C>G	p.Gln102Glu	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.304C>G	p.Gln102Glu	missense_variant	Exon 2 of 12	1	NM_001095.4	ENSP00000400228.3
ASIC1	ENST00000228468.8	c.304C>G	p.Gln102Glu	missense_variant	Exon 2 of 12	1		ENSP00000228468.4
ASIC1	ENST00000550558.5	n.304C>G		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

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.304C>G (p.Q102E) alteration is located in exon 2 (coding exon 1) of the ASIC1 gene. This alteration results from a C to G substitution at nucleotide position 304, causing the glutamine (Q) at amino acid position 102 to be replaced by a glutamic acid (E). 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	0.15
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	-0.049
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.12
Sift	Benign	0.048	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.010	B;B
Vest4		0.21
MutPred		0.61		Gain of disorder (P = 0.1076);Gain of disorder (P = 0.1076);
MVP		0.47
MPC		0.89
ClinPred		0.68	D
GERP RS		4.6
Varity_R		0.35
gMVP		0.88

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: chr12-50452853;