chr4-44713324-T-C

Variant names:

• chr4-44713324-T-C
• rs7670601
• NM_138335.3:c.410-2187A>G

Variant summary

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

The NM_138335.3(GNPDA2):​c.410-2187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,024 control chromosomes in the GnomAD database, including 22,775 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 (22775 hom., cov: 32)
• Consequence: GNPDA2 NM_138335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.92).
• 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 rank	MANE	Protein	UniProt
GNPDA2	NM_138335.3	c.410-2187A>G		intron_variant	Intron 4 of 6	ENST00000295448.8	NP_612208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPDA2	ENST00000295448.8	c.410-2187A>G		intron_variant	Intron 4 of 6	1	NM_138335.3	ENSP00000295448.3

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80602 AN: 151906 Hom.: 22772 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.530 AC: 80630 AN: 152024 Hom.: 22775 Cov.: 32 AF XY: 0.530 AC XY: 39371 AN XY: 74296

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.540

Alfa AF: 0.566 Hom.: 4260

Bravo AF: 0.518

Asia WGS AF: 0.449 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.089
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7670601; hg19: chr4-44715341;