NM_004769.4:c.308C>T

Variant names:

• chr7-151049193-C-T
• rs200735941
• NM_004769.4:c.308C>T

Variant summary

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

The NM_004769.4(ASIC3):​c.308C>T​(p.Thr103Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: ASIC3 NM_004769.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• 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 0 ACMG points.

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.308C>T	p.Thr103Met	missense	Exon 1 of 11	NP_004760.1	Q9UHC3-1
	ASIC3	NM_020321.3		c.308C>T	p.Thr103Met	missense	Exon 1 of 11	NP_064717.1	Q9UHC3-3
	ASIC3	NM_020322.3		c.308C>T	p.Thr103Met	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.308C>T	p.Thr103Met	missense	Exon 1 of 11	ENSP00000344838.5	Q9UHC3-1
	ASIC3	ENST00000297512.12	TSL:1	c.308C>T	p.Thr103Met	missense	Exon 1 of 11	ENSP00000297512.8	Q9UHC3-3
	ASIC3	ENST00000357922.8	TSL:1	c.308C>T	p.Thr103Met	missense	Exon 1 of 10	ENSP00000350600.4	Q9UHC3-2

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000289

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250352 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461144 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 726922

African (AFR) AF: 0.000179 AC: 6 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000306 AC: 34 AN: 1111728

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74494

African (AFR) AF: 0.000289 AC: 12 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15312

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: 10622

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000118 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.18
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.37
MVP		0.83
MPC		0.49
ClinPred		0.88	D
GERP RS		5.1
PromoterAI		-0.027	Neutral
Varity_R		0.48
gMVP		0.50
Mutation Taster		=86/14	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: rs200735941; hg19: chr7-150746280; COSMIC: COSV52511433; COSMIC: COSV52511433;