NM_138335.3:c.410-1301G>T

Variant names:

• chr4-44712438-C-A
• rs12643262
• NM_138335.3:c.410-1301G>T

Variant summary

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

The NM_138335.3(GNPDA2):​c.410-1301G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 152,038 control chromosomes in the GnomAD database, including 534 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 0.077 (534 hom., cov: 31)
• Consequence: GNPDA2 NM_138335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPDA2	NM_138335.3	MANE Select	c.410-1301G>T		intron	N/A	NP_612208.1	Q8TDQ7-1
	GNPDA2	NM_001270880.2		c.308-1301G>T		intron	N/A	NP_001257809.1	Q8TDQ7-5
	GNPDA2	NM_001270881.2		c.200-1301G>T		intron	N/A	NP_001257810.1	Q8TDQ7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPDA2	ENST00000295448.8	TSL:1 MANE Select	c.410-1301G>T		intron	N/A	ENSP00000295448.3	Q8TDQ7-1
	GNPDA2	ENST00000509756.1	TSL:1	c.410-1301G>T		intron	N/A	ENSP00000424061.1	Q8TDQ7-3
	GNPDA2	ENST00000507917.5	TSL:1	c.308-1301G>T		intron	N/A	ENSP00000425868.1	Q8TDQ7-5

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11715 AN: 151922 Hom.: 534 Cov.: 31

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0428

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0686

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

GnomAD4 genome AF: 0.0772 AC: 11731 AN: 152038 Hom.: 534 Cov.: 31 AF XY: 0.0795 AC XY: 5905 AN XY: 74302

African (AFR) AF: 0.0893 AC: 3703 AN: 41478

American (AMR) AF: 0.131 AC: 2003 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 148 AN: 3460

East Asian (EAS) AF: 0.123 AC: 637 AN: 5174

South Asian (SAS) AF: 0.0531 AC: 256 AN: 4822

European-Finnish (FIN) AF: 0.0716 AC: 756 AN: 10566

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0597 AC: 4056 AN: 67970

Other (OTH) AF: 0.0721 AC: 152 AN: 2108

Alfa AF: 0.0743 Hom.: 71

Bravo AF: 0.0826

Asia WGS AF: 0.117 AC: 405 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.40
PhyloP100		-0.74
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: rs12643262; hg19: chr4-44714455;