rs767692106

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001085429.2(TMEM213):c.68C>T(p.Ser23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000383 in 1,594,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

TMEM213
NM_001085429.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.478

Publications

1 publications found

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]

TMEM213 links:

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]

ATP6V0A4 Gene-Disease associations (from GenCC):

renal tubular acidosis, distal, 3, with or without sensorineural hearing loss
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal recessive distal renal tubular acidosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATP6V0A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033955842).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085429.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM213	NM_001085429.2	MANE Select	c.68C>T	p.Ser23Leu	missense	Exon 1 of 3	NP_001078898.1	A2RRL7-1
ATP6V0A4	NM_020632.3	MANE Select	c.-259G>A		5_prime_UTR	Exon 1 of 22	NP_065683.2	Q9HBG4
ATP6V0A4	NM_130840.3		c.-156G>A		5_prime_UTR	Exon 1 of 21	NP_570855.2	Q9HBG4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM213	ENST00000442682.7	TSL:1 MANE Select	c.68C>T	p.Ser23Leu	missense	Exon 1 of 3	ENSP00000390407.2	A2RRL7-1
TMEM213	ENST00000397602.7	TSL:1	c.68C>T	p.Ser23Leu	missense	Exon 1 of 3	ENSP00000380727.3	A2RRL7-3
ATP6V0A4	ENST00000310018.7	TSL:1 MANE Select	c.-259G>A		5_prime_UTR	Exon 1 of 22	ENSP00000308122.2	Q9HBG4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000281

AC:

AN:

213534

AF XY:

0.0000434

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000627

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000388

AC:

AN:

1442454

Hom.:

Cov.:

AF XY:

0.0000503

AC XY:

AN XY:

715458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33158

American (AMR)

AF:

0.0000969

AC:

AN:

41290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25688

East Asian (EAS)

AF:

0.00

AC:

AN:

38830

South Asian (SAS)

AF:

0.00

AC:

AN:

82796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000471

AC:

AN:

1103130

Other (OTH)

AF:

0.00

AC:

AN:

59738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000829

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.2

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.63

M_CAP

Benign

0.0028

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.11

PhyloP100

-0.48

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.94

REVEL

Benign

0.013

Sift

Benign

0.16

Sift4G

Benign

0.34

Polyphen

0.0020

Vest4

0.13

MutPred

0.13

Loss of disorder (P = 0.0622)

MVP

0.030

MPC

0.54

ClinPred

0.065

GERP RS

-1.4

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.025

gMVP

0.13

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over