chr7-151049193-C-A

Variant names:

• chr7-151049193-C-A
• NM_004769.4:c.308C>A

Variant summary

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

The NM_004769.4(ASIC3):​c.308C>A​(p.Thr103Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,144 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASIC3 NM_004769.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 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.308C>A	p.Thr103Lys	missense_variant	Exon 1 of 11	ENST00000349064.10	NP_004760.1
ASIC3	NM_020321.3	c.308C>A	p.Thr103Lys	missense_variant	Exon 1 of 11		NP_064717.1
ASIC3	NM_020322.3	c.308C>A	p.Thr103Lys	missense_variant	Exon 1 of 10		NP_064718.1
ASIC3	NR_046401.1	n.902C>A		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.308C>A	p.Thr103Lys	missense_variant	Exon 1 of 11	1	NM_004769.4	ENSP00000344838.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461144 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726922

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	.;T;.
Eigen	Benign	0.057
Eigen_PC	Benign	-0.0097
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.030	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.73	P;D;P
Vest4		0.37
MutPred		0.65		Loss of phosphorylation at T103 (P = 0.0235);Loss of phosphorylation at T103 (P = 0.0235);Loss of phosphorylation at T103 (P = 0.0235);
MVP		0.78
MPC		0.52
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.51
gMVP		0.61

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: chr7-150746280;