Variant 12-6537943-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002046.7(GAPDH):c.885T>C(p.Phe295Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,607,910 control chromosomes in the GnomAD database, including 51,331 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 0.32 ( 8679 hom., cov: 33)

Exomes 𝑓: 0.23 ( 42652 hom. )

Consequence

GAPDH
NM_002046.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.439

Variant links:

Genes affected

GAPDH (HGNC:4141): (glyceraldehyde-3-phosphate dehydrogenase) This gene encodes a member of the glyceraldehyde-3-phosphate dehydrogenase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The product of this gene catalyzes an important energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamide adenine dinucleotide (NAD). The encoded protein has additionally been identified to have uracil DNA glycosylase activity in the nucleus. Also, this protein contains a peptide that has antimicrobial activity against E. coli, P. aeruginosa, and C. albicans. Studies of a similar protein in mouse have assigned a variety of additional functions including nitrosylation of nuclear proteins, the regulation of mRNA stability, and acting as a transferrin receptor on the cell surface of macrophage. Many pseudogenes similar to this locus are present in the human genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

GAPDH links:

GAPDH (HGNC:):

GAPDH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP7

Synonymous conserved (PhyloP=-0.439 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAPDH	NM_002046.7 linkuse as main transcript	c.885T>C	p.Phe295Phe	synonymous_variant	8/9	ENST00000229239.10	NP_002037.2	P04406-1V9HVZ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAPDH	ENST00000229239.10 linkuse as main transcript	c.885T>C	p.Phe295Phe	synonymous_variant	8/9	1	NM_002046.7	ENSP00000229239.5		P04406-1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47690

AN:

151088

Hom.:

8653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.268

GnomAD3 exomes

AF:

0.278

AC:

68940

AN:

247878

Hom.:

10293

AF XY:

0.268

AC XY:

36089

AN XY:

134512

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.314

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.534

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.235

AC:

342217

AN:

1456710

Hom.:

42652

Cov.:

AF XY:

0.233

AC XY:

169052

AN XY:

724042

show subpopulations

Gnomad4 AFR exome

AF:

0.494

Gnomad4 AMR exome

AF:

0.318

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.523

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.271

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.316

AC:

47769

AN:

151200

Hom.:

8679

Cov.:

AF XY:

0.319

AC XY:

23554

AN XY:

73842

show subpopulations

Gnomad4 AFR

AF:

0.492

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.528

Gnomad4 SAS

AF:

0.280

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.229

Hom.:

1482

Bravo

AF:

0.328

Asia WGS

AF:

0.459

AC:

1592

AN:

3478

EpiCase

AF:

0.195

EpiControl

AF:

0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.27

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over