rs7670601

Variant names:

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

Variant summary

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

The NM_138335.3(GNPDA2):​c.410-2187A>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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.410-2187A>G		intron	N/A	NP_612208.1	Q8TDQ7-1
	GNPDA2	NM_001270880.2		c.308-2187A>G		intron	N/A	NP_001257809.1	Q8TDQ7-5
	GNPDA2	NM_001270881.2		c.200-2187A>G		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.410-2187A>G		intron	N/A	ENSP00000295448.3	Q8TDQ7-1
	GNPDA2	ENST00000509756.1	TSL:1	c.410-2187A>G		intron	N/A	ENSP00000424061.1	Q8TDQ7-3
	GNPDA2	ENST00000507917.5	TSL:1	c.308-2187A>G		intron	N/A	ENSP00000425868.1	Q8TDQ7-5

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

African (AFR) AF: 0.335 AC: 13880 AN: 41490

American (AMR) AF: 0.531 AC: 8100 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3472

East Asian (EAS) AF: 0.413 AC: 2123 AN: 5138

South Asian (SAS) AF: 0.490 AC: 2359 AN: 4814

European-Finnish (FIN) AF: 0.679 AC: 7180 AN: 10572

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43210 AN: 67954

Other (OTH) AF: 0.540 AC: 1141 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.089
DANN	Benign	0.28
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7670601; hg19: chr4-44715341;