chr7-151048979-G-T

Variant names:

• chr7-151048979-G-T
• rs146916223
• NM_004769.4:c.94G>T

Variant summary

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

The NM_004769.4(ASIC3):​c.94G>T​(p.Val32Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V32I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASIC3 NM_004769.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 0 publications found

Genes affected

ASIC3 (HGNC:101): (acid sensing ion channel subunit 3) This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, two hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene is an acid sensor and may play an important role in the detection of lasting pH changes. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 2 has been observed as proton-gated channels sensitive to gadolinium. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC3	NM_004769.4	c.94G>T	p.Val32Phe	missense_variant	Exon 1 of 11	ENST00000349064.10	NP_004760.1
ASIC3	NM_020321.3	c.94G>T	p.Val32Phe	missense_variant	Exon 1 of 11		NP_064717.1
ASIC3	NM_020322.3	c.94G>T	p.Val32Phe	missense_variant	Exon 1 of 10		NP_064718.1
ASIC3	NR_046401.1	n.688G>T		non_coding_transcript_exon_variant	Exon 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC3	ENST00000349064.10	c.94G>T	p.Val32Phe	missense_variant	Exon 1 of 11	1	NM_004769.4	ENSP00000344838.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	.;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.39	N
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.8	L;L;L
PhyloP100		-0.12
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.79	P;P;P
Vest4		0.57
MutPred		0.55		Loss of MoRF binding (P = 0.1446);Loss of MoRF binding (P = 0.1446);Loss of MoRF binding (P = 0.1446);
MVP		0.76
MPC		0.44
ClinPred		0.77	D
GERP RS		1.6
PromoterAI		-0.0080	Neutral
Varity_R		0.55
gMVP		0.50
Mutation Taster		=63/37	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: rs146916223; hg19: chr7-150746066; COSMIC: COSV52509271; COSMIC: COSV52509271;