rs164080

Positions:

• chr5-142011967-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005471.5(GNPDA1):​c.69C>T​(p.Arg23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,612,264 control chromosomes in the GnomAD database, including 179,301 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 0.52 (20768 hom., cov: 31)
  • Exomes 𝑓: 0.46 (158533 hom.)
• Consequence: GNPDA1 NM_005471.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634

Genes affected

GNPDA1 (HGNC:4417): (glucosamine-6-phosphate deaminase 1) Glucosamine-6-phosphate deaminase (EC 3.5.99.6) is an allosteric enzyme that catalyzes the reversible conversion of D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium (Arreola et al., 2003 [PubMed 12965206]).[supplied by OMIM, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.634 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNPDA1	NM_005471.5	c.69C>T	p.Arg23=	synonymous_variant	2/7	ENST00000311337.11
GNPDA1	XM_005268348.2	c.156C>T	p.Arg52=	synonymous_variant	2/7
GNPDA1	XM_006714747.2	c.69C>T	p.Arg23=	synonymous_variant	3/8
GNPDA1	XM_047416582.1	c.69C>T	p.Arg23=	synonymous_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNPDA1	ENST00000311337.11	c.69C>T	p.Arg23=	synonymous_variant	2/7	1	NM_005471.5	P1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78245 AN: 151850 Hom.: 20729 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.503

GnomAD3 exomes AF: 0.482 AC: 121191 AN: 251338 Hom.: 29700 AF XY: 0.478 AC XY: 64892 AN XY: 135848

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.622

Gnomad SAS exome AF: 0.441

Gnomad FIN exome AF: 0.504

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.463 AC: 676640 AN: 1460296 Hom.: 158533 Cov.: 36 AF XY: 0.463 AC XY: 336528 AN XY: 726398

Gnomad4 AFR exome AF: 0.627

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.591

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.515 AC: 78338 AN: 151968 Hom.: 20768 Cov.: 31 AF XY: 0.517 AC XY: 38398 AN XY: 74274

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.505

Alfa AF: 0.471 Hom.: 28576

Bravo AF: 0.516

Asia WGS AF: 0.541 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs164080; hg19: chr5-141391532; COSMIC: COSV60942270;