Variant 1-220074004-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006085.6(BPNT1):c.188C>T(p.Ala63Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

BPNT1
NM_006085.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.19

Variant links:

Genes affected

BPNT1 (HGNC:1096): (3'(2'), 5'-bisphosphate nucleotidase 1) BPNT1, also called bisphosphate 3-prime-nucleotidase, or BPntase, is a member of a magnesium-dependent phosphomonoesterase family. Lithium, a major drug used to treat manic depression, acts as an uncompetitive inhibitor of BPntase. The predicted human protein is 92% identical to mouse BPntase. BPntase's physiologic role in nucleotide metabolism may be regulated by inositol signaling pathways. The inhibition of human BPntase may account for lithium-induced nephrotoxicity. [provided by RefSeq, Jul 2008]

BPNT1 links:

BPNT1 (HGNC:):

BPNT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29294908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPNT1	NM_006085.6 linkuse as main transcript	c.188C>T	p.Ala63Val	missense_variant	3/9	ENST00000322067.12	NP_006076.4	O95861-1V9HWF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPNT1	ENST00000322067.12 linkuse as main transcript	c.188C>T	p.Ala63Val	missense_variant	3/9	1	NM_006085.6	ENSP00000318852.7		O95861-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249488

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135350

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 SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727196

show subpopulations

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:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.188C>T (p.A63V) alteration is located in exon 3 (coding exon 2) of the BPNT1 gene. This alteration results from a C to T substitution at nucleotide position 188, causing the alanine (A) at amino acid position 63 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;.;T;T;T;.;T;.;.

Eigen

Benign

0.053

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D;D;.;D;D;D;D;D

M_CAP

Benign

0.0068

MetaRNN

Benign

0.29

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.8

.;M;M;M;.;.;.;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.7

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.16

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T;T;.;T;.

Polyphen

0.0020, 0.025

.;.;B;B;B;.;.;.;.

Vest4

0.16

MutPred

0.49

.;Gain of methylation at K65 (P = 0.0764);Gain of methylation at K65 (P = 0.0764);Gain of methylation at K65 (P = 0.0764);Gain of methylation at K65 (P = 0.0764);Gain of methylation at K65 (P = 0.0764);Gain of methylation at K65 (P = 0.0764);.;Gain of methylation at K65 (P = 0.0764);

MVP

0.25

MPC

0.33

ClinPred

0.45

GERP RS

4.5

Varity_R

0.22

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over