chr7-134661843-G-T

Variant names:

• chr7-134661843-G-T
• rs376210775
• NM_001724.5:c.336G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001724.5(BPGM):​c.336G>T​(p.Val112Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V112V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BPGM NM_001724.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hemolytic anemia due to diphosphoglycerate mutase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

LOC124901750 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=2.86 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001724.5. 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
	BPGM	NM_001724.5	MANE Select	c.336G>T	p.Val112Val	synonymous	Exon 2 of 3	NP_001715.1	P07738
	BPGM	NM_001293085.2		c.336G>T	p.Val112Val	synonymous	Exon 3 of 4	NP_001280014.1	P07738
	BPGM	NM_199186.3		c.336G>T	p.Val112Val	synonymous	Exon 3 of 4	NP_954655.1	A0A024R782

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPGM	ENST00000344924.8	TSL:1 MANE Select	c.336G>T	p.Val112Val	synonymous	Exon 2 of 3	ENSP00000342032.3	P07738
	BPGM	ENST00000393132.2	TSL:5	c.336G>T	p.Val112Val	synonymous	Exon 3 of 4	ENSP00000376840.2	P07738
	BPGM	ENST00000418040.5	TSL:5	c.336G>T	p.Val112Val	synonymous	Exon 3 of 4	ENSP00000399838.1	P07738

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455948 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723576

African (AFR) AF: 0.00 AC: 0 AN: 33192

American (AMR) AF: 0.00 AC: 0 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25760

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108438

Other (OTH) AF: 0.00 AC: 0 AN: 60040

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.3
DANN	Benign	0.72
PhyloP100		2.9

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

Other links and lift over

dbSNP: rs376210775; hg19: chr7-134346595;