rs4484337

Positions:

• chr4-44709530-C-G

Variant summary

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

The NM_138335.3(GNPDA2):​c.594+1423G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,952 control chromosomes in the GnomAD database, including 22,461 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 (22461 hom., cov: 31)
• Consequence: GNPDA2 NM_138335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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=-0.5).
• 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	UniProt
GNPDA2	NM_138335.3	c.594+1423G>C		intron_variant		ENST00000295448.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNPDA2	ENST00000295448.8	c.594+1423G>C		intron_variant		1	NM_138335.3	P1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79937 AN: 151834 Hom.: 22458 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.526 AC: 79967 AN: 151952 Hom.: 22461 Cov.: 31 AF XY: 0.525 AC XY: 39008 AN XY: 74266

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.538

Alfa AF: 0.568 Hom.: 3165

Bravo AF: 0.511

Asia WGS AF: 0.440 AC: 1530 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.0
DANN	Benign	0.91

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: rs4484337; hg19: chr4-44711547; COSMIC: COSV54948318; COSMIC: COSV54948318;