NM_001692.4:c.1469C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001692.4(ATP6V1B1):c.1469C>T(p.Pro490Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,613,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

ATP6V1B1
NM_001692.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: 7.91

Publications

1 publications found

Variant links:

Genes affected

ATP6V1B1 (HGNC:853): (ATPase H+ transporting V1 subunit B1) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle 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. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of two V1 domain B subunit isoforms and is found in the kidney. Mutations in this gene cause distal renal tubular acidosis associated with sensorineural deafness. [provided by RefSeq, Jul 2008]

ATP6V1B1 links:

ENSG00000258881 (HGNC:):

ENSG00000258881 links:

VAX2 (HGNC:12661): (ventral anterior homeobox 2) This gene encodes a homeobox protein and is almost exclusively expressed in the ventral portion of the retina during development. In mouse studies, this gene was found to be required for the correct formation of the optic fissure and other aspects of retinal development. [provided by RefSeq, Sep 2008]

VAX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.16405043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001692.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B1	NM_001692.4	MANE Select	c.1469C>T	p.Pro490Leu	missense	Exon 14 of 14	NP_001683.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V1B1	ENST00000234396.10	TSL:1 MANE Select	c.1469C>T	p.Pro490Leu	missense	Exon 14 of 14	ENSP00000234396.4	P15313
ENSG00000258881	ENST00000606025.5	TSL:5	c.476-22615G>A		intron	N/A	ENSP00000475641.1	U3KQ87
ATP6V1B1	ENST00000872157.1		c.1505C>T	p.Pro502Leu	missense	Exon 14 of 14	ENSP00000542216.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152208

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:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000152

AC:

AN:

250586

AF XY:

0.000155

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000766

AC:

112

AN:

1461206

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

726912

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00121

AC:

104

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.000116

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.0000656

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Renal tubular acidosis with progressive nerve deafness (3)

ATP6V1B1-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.76

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.16

MetaSVM

Uncertain

0.14

MutationAssessor

Pathogenic

3.3

PhyloP100

7.9

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.019

Polyphen

0.94

Vest4

0.79

MutPred

0.52

Gain of helix (P = 0.0496)

MVP

0.89

MPC

0.80

ClinPred

0.60

GERP RS

3.1

Varity_R

0.59

gMVP

0.85

Mutation Taster

=24/76

disease causing

(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