chr7-138798112-G-T

Variant names:

• chr7-138798112-G-T
• rs138299222
• NM_001085429.2:c.8G>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.8G>T​(p.Arg3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,852 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: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM213 NM_001085429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.26

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=0.040140957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM213	NM_001085429.2	c.8G>T	p.Arg3Leu	missense_variant	Exon 1 of 3	ENST00000442682.7	NP_001078898.1
ATP6V0A4	NM_020632.3	c.-199C>A		5_prime_UTR_variant	Exon 1 of 22	ENST00000310018.7	NP_065683.2
ATP6V0A4	NM_130840.3	c.-96C>A		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.8G>T	p.Arg3Leu	missense_variant	Exon 1 of 3	1	NM_001085429.2	ENSP00000390407.2
ATP6V0A4	ENST00000310018.7	c.-199C>A		5_prime_UTR_variant	Exon 1 of 22	1	NM_020632.3	ENSP00000308122.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000453 AC: 1 AN: 220852 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 119668

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445852 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717616

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000237

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: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0050
DANN	Benign	0.88
DEOGEN2	Benign	0.017	.;T;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.54	T;T;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.040	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.7	N;N;N;D
REVEL	Benign	0.013
Sift	Benign	0.076	T;T;T;D
Sift4G	Uncertain	0.047	D;D;D;D
Polyphen		0.0010	B;B;.;.
Vest4		0.091
MutPred		0.22		Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);
MVP		0.030
MPC		0.35
ClinPred		0.069	T
GERP RS		-9.0
Varity_R		0.051
gMVP		0.31

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: rs138299222; hg19: chr7-138482857;