Variant 7-134661754-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001724.5(BPGM):c.247A>T(p.Ser83Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BPGM
NM_001724.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

Variant links:

Genes affected

BPGM (HGNC:1093): (bisphosphoglycerate mutase) 2,3-diphosphoglycerate (2,3-DPG) is a small molecule found at high concentrations in red blood cells where it binds to and decreases the oxygen affinity of hemoglobin. This gene encodes a multifunctional enzyme that catalyzes 2,3-DPG synthesis via its synthetase activity, and 2,3-DPG degradation via its phosphatase activity. The enzyme also has phosphoglycerate phosphomutase activity. Deficiency of this enzyme increases the affinity of cells for oxygen. Mutations in this gene result in hemolytic anemia. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

BPGM links:

LOC124901750 (HGNC:):

LOC124901750 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a chain Bisphosphoglycerate mutase (size 257) in uniprot entity PMGE_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001724.5

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPGM	NM_001724.5 linkuse as main transcript	c.247A>T	p.Ser83Cys	missense_variant	2/3	ENST00000344924.8	NP_001715.1
LOC124901750	XR_007060537.1 linkuse as main transcript	n.29222-41806T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BPGM	ENST00000344924.8 linkuse as main transcript	c.247A>T	p.Ser83Cys	missense_variant	2/3	1	NM_001724.5	ENSP00000342032	P1
BPGM	ENST00000393132.2 linkuse as main transcript	c.247A>T	p.Ser83Cys	missense_variant	3/4	5		ENSP00000376840	P1
BPGM	ENST00000418040.5 linkuse as main transcript	c.247A>T	p.Ser83Cys	missense_variant	3/4	5		ENSP00000399838	P1
BPGM	ENST00000443095.1 linkuse as main transcript			downstream_gene_variant		4		ENSP00000403050

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Sep 12, 2023

The c.247A>T (p.S83C) alteration is located in exon 3 (coding exon 1) of the BPGM gene. This alteration results from a A to T substitution at nucleotide position 247, causing the serine (S) at amino acid position 83 to be replaced by a cysteine (C). 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

0.064

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;T;T

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

.;.;D

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Uncertain

0.027

MutationAssessor

Benign

1.5

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.50

MutPred

0.49

Loss of disorder (P = 0.0276);Loss of disorder (P = 0.0276);Loss of disorder (P = 0.0276);

MVP

0.91

MPC

0.96

ClinPred

1.0

GERP RS

6.0

Varity_R

0.71

gMVP

0.80

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over