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GeneBe

7-138798169-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001085429.2(TMEM213):c.65A>G(p.His22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Consequence

TMEM213
NM_001085429.2 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.154
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.084671736).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMEM213NM_001085429.2 linkuse as main transcriptc.65A>G p.His22Arg missense_variant 1/3 ENST00000442682.7
ATP6V0A4NM_020632.3 linkuse as main transcriptc.-256T>C 5_prime_UTR_variant 1/22 ENST00000310018.7
ATP6V0A4NM_130840.3 linkuse as main transcriptc.-153T>C 5_prime_UTR_variant 1/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMEM213ENST00000442682.7 linkuse as main transcriptc.65A>G p.His22Arg missense_variant 1/31 NM_001085429.2 P4A2RRL7-1
ATP6V0A4ENST00000310018.7 linkuse as main transcriptc.-256T>C 5_prime_UTR_variant 1/221 NM_020632.3 P1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 15, 2023The c.65A>G (p.H22R) alteration is located in exon 1 (coding exon 1) of the TMEM213 gene. This alteration results from a A to G substitution at nucleotide position 65, causing the histidine (H) at amino acid position 22 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
Cadd
Benign
3.2
Dann
Benign
0.88
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.58
T;T;T;T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.085
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;M;M;M
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-4.0
D;D;D;D
REVEL
Benign
0.040
Sift
Benign
0.16
T;T;D;D
Sift4G
Benign
0.89
T;T;D;T
Polyphen
0.0020
B;B;.;.
Vest4
0.15
MutPred
0.16
Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);
MVP
0.014
MPC
0.59
ClinPred
0.37
T
GERP RS
-1.9
Varity_R
0.097
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr7-138482914; API