chr7-138798172-C-G

Variant names:

• chr7-138798172-C-G
• NM_001085429.2:c.68C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001085429.2(TMEM213):​c.68C>G​(p.Ser23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: -0.478

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07421866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM213	NM_001085429.2	c.68C>G	p.Ser23Trp	missense_variant	Exon 1 of 3	ENST00000442682.7	NP_001078898.1
ATP6V0A4	NM_020632.3	c.-259G>C		5_prime_UTR_variant	Exon 1 of 22	ENST00000310018.7	NP_065683.2
ATP6V0A4	NM_130840.3	c.-156G>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.68C>G	p.Ser23Trp	missense_variant	Exon 1 of 3	1	NM_001085429.2	ENSP00000390407.2
ATP6V0A4	ENST00000310018.7	c.-259G>C		5_prime_UTR_variant	Exon 1 of 22	1	NM_020632.3	ENSP00000308122.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442454 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715458

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: 9.07e-7

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	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	.;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.074	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;L;L
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D;N;D;D
REVEL	Benign	0.016
Sift	Uncertain	0.025	D;T;D;D
Sift4G	Uncertain	0.030	D;T;D;D
Polyphen		0.0020	B;B;.;.
Vest4		0.27
MutPred		0.24		Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);
MVP		0.030
MPC		1.1
ClinPred		0.86	D
GERP RS		-1.4
Varity_R		0.051
gMVP		0.24

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: chr7-138482917;