1-10413139-C-T

Variant names:

• chr1-10413139-C-T
• rs2229687
• NM_002631.4:c.732C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002631.4(PGD):​c.732C>T​(p.Asp244Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,613,230 control chromosomes in the GnomAD database, including 85,981 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8425 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77556 hom.)
• Consequence: PGD NM_002631.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613
• Publications: 22 publications found

Genes affected

PGD (HGNC:8891): (phosphogluconate dehydrogenase) 6-phosphogluconate dehydrogenase is the second dehydrogenase in the pentose phosphate shunt. Deficiency of this enzyme is generally asymptomatic, and the inheritance of this disorder is autosomal dominant. Hemolysis results from combined deficiency of 6-phosphogluconate dehydrogenase and 6-phosphogluconolactonase suggesting a synergism of the two enzymopathies. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.613 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002631.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGD	NM_002631.4	MANE Select	c.732C>T	p.Asp244Asp	synonymous	Exon 8 of 13	NP_002622.2
	PGD	NM_001304452.2		c.693C>T	p.Asp231Asp	synonymous	Exon 8 of 13	NP_001291381.1
	PGD	NM_001304451.2		c.666C>T	p.Asp222Asp	synonymous	Exon 7 of 12	NP_001291380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGD	ENST00000270776.13	TSL:1 MANE Select	c.732C>T	p.Asp244Asp	synonymous	Exon 8 of 13	ENSP00000270776.8
	PGD	ENST00000460189.1	TSL:2	c.654C>T	p.Asp218Asp	synonymous	Exon 6 of 6	ENSP00000467362.1
	PGD	ENST00000483936.5	TSL:5	c.297C>T	p.Asp99Asp	synonymous	Exon 4 of 6	ENSP00000466156.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50121 AN: 151940 Hom.: 8394 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.329

GnomAD2 exomes AF: 0.327 AC: 82324 AN: 251402 AF XY: 0.321

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.323

Gnomad EAS exome AF: 0.363

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.325 AC: 474317 AN: 1461172 Hom.: 77556 Cov.: 34 AF XY: 0.322 AC XY: 234321 AN XY: 726918

African (AFR) AF: 0.325 AC: 10867 AN: 33468

American (AMR) AF: 0.379 AC: 16942 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8453 AN: 26128

East Asian (EAS) AF: 0.336 AC: 13356 AN: 39694

South Asian (SAS) AF: 0.259 AC: 22328 AN: 86240

European-Finnish (FIN) AF: 0.350 AC: 18664 AN: 53394

Middle Eastern (MID) AF: 0.296 AC: 1705 AN: 5762

European-Non Finnish (NFE) AF: 0.326 AC: 362015 AN: 1111408

Other (OTH) AF: 0.331 AC: 19987 AN: 60362

GnomAD4 genome AF: 0.330 AC: 50203 AN: 152058 Hom.: 8425 Cov.: 32 AF XY: 0.331 AC XY: 24598 AN XY: 74298

African (AFR) AF: 0.327 AC: 13552 AN: 41482

American (AMR) AF: 0.370 AC: 5647 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1830 AN: 5172

South Asian (SAS) AF: 0.277 AC: 1331 AN: 4812

European-Finnish (FIN) AF: 0.345 AC: 3635 AN: 10544

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21836 AN: 67990

Other (OTH) AF: 0.334 AC: 704 AN: 2108

Alfa AF: 0.327 Hom.: 9211

Bravo AF: 0.335

Asia WGS AF: 0.347 AC: 1204 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.33
DANN	Benign	0.15
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=96/4	polymorphism (auto)

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: rs2229687; hg19: chr1-10473196; COSMIC: COSV54620659; COSMIC: COSV54620659;