chr7-151049265-G-T

Position:

• chr7-151049265-G-T

Variant summary

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

The NM_004769.4(ASIC3):​c.380G>T​(p.Arg127Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R127H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASIC3 NM_004769.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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

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=0.16352066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC3	NM_004769.4	c.380G>T	p.Arg127Leu	missense_variant	1/11	ENST00000349064.10
ASIC3	NM_020321.3	c.380G>T	p.Arg127Leu	missense_variant	1/11
ASIC3	NM_020322.3	c.380G>T	p.Arg127Leu	missense_variant	1/10
ASIC3	NR_046401.1	n.974G>T		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC3	ENST00000349064.10	c.380G>T	p.Arg127Leu	missense_variant	1/11	1	NM_004769.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L;L;L
MutationTaster	Benign	0.77	N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.012	B;P;B
Vest4		0.36
MutPred		0.52		Loss of methylation at R127 (P = 0.0391);Loss of methylation at R127 (P = 0.0391);Loss of methylation at R127 (P = 0.0391);
MVP		0.58
MPC		0.39
ClinPred		0.34	T
GERP RS		4.4
Varity_R		0.067
gMVP		0.65

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: chr7-150746352;