chr12-6537813-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002046.7(GAPDH):​c.755C>T​(p.Pro252Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,656 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GAPDH
NM_002046.7 missense

Scores

2
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.83
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37934107).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GAPDHNM_002046.7 linkc.755C>T p.Pro252Leu missense_variant Exon 8 of 9 ENST00000229239.10 NP_002037.2 P04406-1V9HVZ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GAPDHENST00000229239.10 linkc.755C>T p.Pro252Leu missense_variant Exon 8 of 9 1 NM_002046.7 ENSP00000229239.5 P04406-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459656
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
726138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
D;.;D;D;.;.
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.84
.;T;.;T;.;T
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.38
T;T;T;T;T;T
MetaSVM
Uncertain
0.0078
D
MutationAssessor
Pathogenic
3.6
H;.;H;H;.;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.9
D;D;D;D;D;.
REVEL
Benign
0.29
Sift
Uncertain
0.0020
D;D;D;D;D;.
Sift4G
Uncertain
0.017
D;D;D;D;D;D
Polyphen
0.51
P;P;P;P;.;.
Vest4
0.25
MutPred
0.37
Loss of methylation at K251 (P = 0.0564);.;Loss of methylation at K251 (P = 0.0564);Loss of methylation at K251 (P = 0.0564);.;.;
MVP
0.77
MPC
1.4
ClinPred
0.99
D
GERP RS
5.0
Varity_R
0.58
gMVP
0.68

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs1946517126; hg19: chr12-6646979; API