1-10413139-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGD	NM_002631.4	c.732C>T	p.Asp244Asp	synonymous_variant	Exon 8 of 13	ENST00000270776.13	NP_002622.2
PGD	NM_001304452.2	c.693C>T	p.Asp231Asp	synonymous_variant	Exon 8 of 13		NP_001291381.1
PGD	NM_001304451.2	c.666C>T	p.Asp222Asp	synonymous_variant	Exon 7 of 12		NP_001291380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGD	ENST00000270776.13	c.732C>T	p.Asp244Asp	synonymous_variant	Exon 8 of 13	1	NM_002631.4	ENSP00000270776.8
PGD	ENST00000460189.1	c.654C>T	p.Asp218Asp	synonymous_variant	Exon 6 of 6	2		ENSP00000467362.1
PGD	ENST00000483936.5	c.297C>T	p.Asp99Asp	synonymous_variant	Exon 4 of 6	5		ENSP00000466156.1
PGD	ENST00000493288.1	n.306C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

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

GnomAD3 exomes AF: 0.327 AC: 82324 AN: 251402 Hom.: 13763 AF XY: 0.321 AC XY: 43623 AN XY: 135886

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 SAS exome AF: 0.261

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

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.331

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.334

Alfa AF: 0.326 Hom.: 6855

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.33
DANN	Benign	0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

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