rs16857402

Variant names:

• chr4-44704436-T-C
• rs16857402
• ENST00000509756.1:c.*3305A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000295448.8(GNPDA2):​c.770-1294A>G variant causes a intron 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 ENST00000295448.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000295448.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPDA2	NM_138335.3	MANE Select	c.770-1294A>G		intron	N/A	NP_612208.1
	GNPDA2	NM_001270880.2		c.668-1294A>G		intron	N/A	NP_001257809.1
	GNPDA2	NM_001270881.2		c.560-1294A>G		intron	N/A	NP_001257810.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPDA2	ENST00000509756.1	TSL:1	c.*3305A>G		3_prime_UTR	Exon 6 of 6	ENSP00000424061.1
	GNPDA2	ENST00000295448.8	TSL:1 MANE Select	c.770-1294A>G		intron	N/A	ENSP00000295448.3
	GNPDA2	ENST00000507917.5	TSL:1	c.668-1294A>G		intron	N/A	ENSP00000425868.1

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

African (AFR) AF: 0.243 AC: 3454 AN: 14220

American (AMR) AF: 0.159 AC: 139 AN: 874

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 1245 AN: 4624

East Asian (EAS) AF: 0.218 AC: 713 AN: 3264

South Asian (SAS) AF: 0.321 AC: 4722 AN: 14728

European-Finnish (FIN) AF: 0.185 AC: 48 AN: 260

Middle Eastern (MID) AF: 0.328 AC: 480 AN: 1464

European-Non Finnish (NFE) AF: 0.221 AC: 152865 AN: 692458

Other (OTH) AF: 0.232 AC: 5735 AN: 24688

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

African (AFR) AF: 0.240 AC: 9964 AN: 41474

American (AMR) AF: 0.172 AC: 2623 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1119 AN: 5174

South Asian (SAS) AF: 0.337 AC: 1627 AN: 4822

European-Finnish (FIN) AF: 0.155 AC: 1643 AN: 10598

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15611 AN: 67878

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.226 Hom.: 1413

Bravo AF: 0.222

Asia WGS AF: 0.218 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.59
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16857402; hg19: chr4-44706453;