rs10020551

Positions:

• chr4-44705798-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000509756.1(GNPDA2):​c.*1943C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,580 control chromosomes in the GnomAD database, including 22,406 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 0.53 (22406 hom., cov: 31)
  • Exomes 𝑓: 0.38 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNPDA2 ENST00000509756.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

Genes affected

GNPDA2 (HGNC:21526): (glucosamine-6-phosphate deaminase 2) The protein encoded by this gene is an allosteric enzyme that catalyzes the reversible reaction converting D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium. Variations of this gene have been reported to be associated with influencing body mass index and susceptibility to obesity. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPDA2	NM_138335.3	c.769+1954C>A		intron_variant		ENST00000295448.8	NP_612208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPDA2	ENST00000295448.8	c.769+1954C>A		intron_variant		1	NM_138335.3	ENSP00000295448	P1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79736 AN: 151462 Hom.: 22403 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.537

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.375 AC: 3 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.375 AC XY: 3 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.526 AC: 79766 AN: 151580 Hom.: 22406 Cov.: 31 AF XY: 0.525 AC XY: 38911 AN XY: 74084

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.534

Alfa AF: 0.577 Hom.: 5613

Bravo AF: 0.511

Asia WGS AF: 0.441 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.81

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: rs10020551; hg19: chr4-44707815;