rs164080

Variant names:

• chr5-142011967-G-A
• rs164080
• NM_005471.5:c.69C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005471.5(GNPDA1):​c.69C>T​(p.Arg23Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,612,264 control chromosomes in the GnomAD database, including 179,301 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 0.52 (20768 hom., cov: 31)
  • Exomes 𝑓: 0.46 (158533 hom.)
• Consequence: GNPDA1 NM_005471.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634
• Publications: 33 publications found

Genes affected

GNPDA1 (HGNC:4417): (glucosamine-6-phosphate deaminase 1) Glucosamine-6-phosphate deaminase (EC 3.5.99.6) is an allosteric enzyme that catalyzes the reversible conversion of D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium (Arreola et al., 2003 [PubMed 12965206]).[supplied by OMIM, Jan 2010]

ENSG00000308869 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.634 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNPDA1	NM_005471.5	c.69C>T	p.Arg23Arg	synonymous_variant	Exon 2 of 7	ENST00000311337.11	NP_005462.1
GNPDA1	XM_005268348.2	c.156C>T	p.Arg52Arg	synonymous_variant	Exon 2 of 7		XP_005268405.1
GNPDA1	XM_006714747.2	c.69C>T	p.Arg23Arg	synonymous_variant	Exon 3 of 8		XP_006714810.1
GNPDA1	XM_047416582.1	c.69C>T	p.Arg23Arg	synonymous_variant	Exon 3 of 8		XP_047272538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPDA1	ENST00000311337.11	c.69C>T	p.Arg23Arg	synonymous_variant	Exon 2 of 7	1	NM_005471.5	ENSP00000311876.6

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78245 AN: 151850 Hom.: 20729 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.503

GnomAD2 exomes AF: 0.482 AC: 121191 AN: 251338 AF XY: 0.478

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.622

Gnomad FIN exome AF: 0.504

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.463 AC: 676640 AN: 1460296 Hom.: 158533 Cov.: 36 AF XY: 0.463 AC XY: 336528 AN XY: 726398

African (AFR) AF: 0.627 AC: 20982 AN: 33448

American (AMR) AF: 0.413 AC: 18457 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 12842 AN: 26124

East Asian (EAS) AF: 0.591 AC: 23444 AN: 39674

South Asian (SAS) AF: 0.440 AC: 37924 AN: 86190

European-Finnish (FIN) AF: 0.501 AC: 26744 AN: 53390

Middle Eastern (MID) AF: 0.552 AC: 3178 AN: 5758

European-Non Finnish (NFE) AF: 0.454 AC: 504083 AN: 1110668

Other (OTH) AF: 0.480 AC: 28986 AN: 60340

GnomAD4 genome AF: 0.515 AC: 78338 AN: 151968 Hom.: 20768 Cov.: 31 AF XY: 0.517 AC XY: 38398 AN XY: 74274

African (AFR) AF: 0.629 AC: 26043 AN: 41408

American (AMR) AF: 0.466 AC: 7110 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1731 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3152 AN: 5162

South Asian (SAS) AF: 0.463 AC: 2224 AN: 4806

European-Finnish (FIN) AF: 0.507 AC: 5357 AN: 10576

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31223 AN: 67968

Other (OTH) AF: 0.505 AC: 1066 AN: 2112

Alfa AF: 0.476 Hom.: 38391

Bravo AF: 0.516

Asia WGS AF: 0.541 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs164080; hg19: chr5-141391532; COSMIC: COSV60942270;