chr7-151048929-C-T

Variant names:

• chr7-151048929-C-T
• rs116014003
• NM_004769.4:c.44C>T

Variant summary

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

The NM_004769.4(ASIC3):​c.44C>T​(p.Ser15Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000014 in 1,570,470 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ASIC3 NM_004769.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31
• Publications: 1 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004769.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC3	NM_004769.4	MANE Select	c.44C>T	p.Ser15Leu	missense	Exon 1 of 11	NP_004760.1	Q9UHC3-1
	ASIC3	NM_020321.3		c.44C>T	p.Ser15Leu	missense	Exon 1 of 11	NP_064717.1	Q9UHC3-3
	ASIC3	NM_020322.3		c.44C>T	p.Ser15Leu	missense	Exon 1 of 10	NP_064718.1	Q9UHC3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC3	ENST00000349064.10	TSL:1 MANE Select	c.44C>T	p.Ser15Leu	missense	Exon 1 of 11	ENSP00000344838.5	Q9UHC3-1
	ASIC3	ENST00000297512.12	TSL:1	c.44C>T	p.Ser15Leu	missense	Exon 1 of 11	ENSP00000297512.8	Q9UHC3-3
	ASIC3	ENST00000357922.8	TSL:1	c.44C>T	p.Ser15Leu	missense	Exon 1 of 10	ENSP00000350600.4	Q9UHC3-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000181 AC: 4 AN: 220532 AF XY: 0.0000169

Gnomad AFR exome AF: 0.0000660

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000143

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000999

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000127 AC: 18 AN: 1418118 Hom.: 0 Cov.: 31 AF XY: 0.00000859 AC XY: 6 AN XY: 698696

African (AFR) AF: 0.000122 AC: 4 AN: 32840

American (AMR) AF: 0.00 AC: 0 AN: 42410

Ashkenazi Jewish (ASJ) AF: 0.0000430 AC: 1 AN: 23278

East Asian (EAS) AF: 0.00 AC: 0 AN: 39158

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5566

European-Non Finnish (NFE) AF: 0.00000920 AC: 10 AN: 1086430

Other (OTH) AF: 0.0000171 AC: 1 AN: 58496

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74500

African (AFR) AF: 0.0000962 AC: 4 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.026	D
Polyphen		0.97	D
Vest4		0.48
MutPred		0.35		Loss of disorder (P = 0.0063)
MVP		0.76
MPC		0.39
ClinPred		0.79	D
GERP RS		4.9
PromoterAI		0.0088	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.19
gMVP		0.32
Mutation Taster		=69/31	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: rs116014003; hg19: chr7-150746016;