chr4-44704436-T-C

Position:

• chr4-44704436-T-C

Variant summary

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

The ENST00000509756(GNPDA2):​c.*3305A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 908,530 control chromosomes in the GnomAD database, including 23,307 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 0.23 (4069 hom., cov: 32)
  • Exomes 𝑓: 0.22 (19238 hom.)
• Consequence: GNPDA2 ENST00000509756 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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]

ENSG00000272936 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPDA2	NM_138335.3	c.770-1294A>G		intron_variant		ENST00000295448.8	NP_612208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPDA2	ENST00000295448.8	c.770-1294A>G		intron_variant		1	NM_138335.3	ENSP00000295448.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34246 AN: 151832 Hom.: 4063 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.224 AC: 169401 AN: 756580 Hom.: 19238 Cov.: 11 AF XY: 0.225 AC XY: 79027 AN XY: 351142

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.226 AC: 34270 AN: 151950 Hom.: 4069 Cov.: 32 AF XY: 0.222 AC XY: 16514 AN XY: 74276

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.231

Alfa AF: 0.228 Hom.: 716

Bravo AF: 0.222

Asia WGS AF: 0.218 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.59

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: rs16857402; hg19: chr4-44706453;