rs759335247

Variant names:

• chr7-138798181-C-G
• rs759335247
• NM_001085429.2:c.77C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-138798181-C-G
• chr7-138798181-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001085429.2(TMEM213):​c.77C>G​(p.Ser26Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
• Consequence: TMEM213 NM_001085429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

Genes affected

TMEM213 (HGNC:27220): (transmembrane protein 213) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATP6V0A4 (HGNC:866): (ATPase H+ transporting V0 subunit a4) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. This gene is one of four genes in man and mouse that encode different isoforms of the a subunit. Alternatively spliced transcript variants encoding the same protein have been described. Mutations in this gene are associated with renal tubular acidosis associated with preserved hearing. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045936316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM213	NM_001085429.2	c.77C>G	p.Ser26Trp	missense_variant	Exon 1 of 3	ENST00000442682.7	NP_001078898.1
ATP6V0A4	NM_020632.3	c.-268G>C		5_prime_UTR_variant	Exon 1 of 22	ENST00000310018.7	NP_065683.2
ATP6V0A4	NM_130840.3	c.-165G>C		5_prime_UTR_variant	Exon 1 of 21		NP_570855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM213	ENST00000442682.7	c.77C>G	p.Ser26Trp	missense_variant	Exon 1 of 3	1	NM_001085429.2	ENSP00000390407.2
ATP6V0A4	ENST00000310018.7	c.-268G>C		5_prime_UTR_variant	Exon 1 of 22	1	NM_020632.3	ENSP00000308122.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151996 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151996 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74222

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.061	.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.43	T;T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.046	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.5	D;N;N;N
REVEL	Benign	0.053
Sift	Uncertain	0.020	D;D;D;D
Sift4G	Benign	0.062	T;T;D;T
Polyphen		0.0010	B;B;.;.
Vest4		0.25
MutPred		0.30		Loss of disorder (P = 2e-04);Loss of disorder (P = 2e-04);Loss of disorder (P = 2e-04);Loss of disorder (P = 2e-04);
MVP		0.048
MPC		1.1
ClinPred		0.20	T
GERP RS		-2.6
Varity_R		0.075
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs759335247; hg19: chr7-138482926;