7-134661622-C-G

Variant names:

• chr7-134661622-C-G
• NM_001724.5:c.115C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001724.5(BPGM):​c.115C>G​(p.Arg39Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BPGM NM_001724.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92

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]

LOC124901750 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
BPGM	NM_001724.5	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 3	ENST00000344924.8	NP_001715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPGM	ENST00000344924.8	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 3	1	NM_001724.5	ENSP00000342032.3
BPGM	ENST00000393132.2	c.115C>G	p.Arg39Gly	missense_variant	Exon 3 of 4	5		ENSP00000376840.2
BPGM	ENST00000418040.5	c.115C>G	p.Arg39Gly	missense_variant	Exon 3 of 4	5		ENSP00000399838.1
BPGM	ENST00000443095.1	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 2	4		ENSP00000403050.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727228

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;T;T;.
Eigen	Benign	0.026
Eigen_PC	Benign	0.063
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	.;.;D;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.8	M;M;M;.
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Uncertain	0.41
Sift	Benign	0.20	T;T;T;D
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.45	B;B;B;.
Vest4		0.50
MutPred		0.54		Loss of methylation at R39 (P = 0.0184);Loss of methylation at R39 (P = 0.0184);Loss of methylation at R39 (P = 0.0184);Loss of methylation at R39 (P = 0.0184);
MVP		0.82
MPC		0.49
ClinPred		0.87	D
GERP RS		3.3
Varity_R		0.77
gMVP		0.66

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.

Other links and lift over

hg19: chr7-134346374;