12-6534150-T-C

Variant names:

• chr12-6534150-T-C
• rs6489721
• ENST00000920777.1:c.-182T>C

Variant summary

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

The ENST00000920777.1(GAPDH):​c.-182T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 153,780 control chromosomes in the GnomAD database, including 6,356 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 0.27 (6309 hom., cov: 33)
  • Exomes 𝑓: 0.19 (47 hom.)
• Consequence: GAPDH ENST00000920777.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 23 publications found

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-DT (HGNC:55492): (GAPDH divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000920777.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDH	ENST00000920777.1		c.-182T>C		5_prime_UTR	Exon 1 of 9	ENSP00000590836.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41717 AN: 151934 Hom.: 6293 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.192 AC: 332 AN: 1728 Hom.: 47 Cov.: 0 AF XY: 0.201 AC XY: 230 AN XY: 1144

African (AFR) AF: 0.286 AC: 4 AN: 14

American (AMR) AF: 0.196 AC: 18 AN: 92

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 2 AN: 8

East Asian (EAS) AF: 0.375 AC: 6 AN: 16

South Asian (SAS) AF: 0.190 AC: 72 AN: 378

European-Finnish (FIN) AF: 0.143 AC: 6 AN: 42

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.188 AC: 204 AN: 1084

Other (OTH) AF: 0.233 AC: 20 AN: 86

GnomAD4 genome AF: 0.275 AC: 41776 AN: 152052 Hom.: 6309 Cov.: 33 AF XY: 0.278 AC XY: 20637 AN XY: 74350

African (AFR) AF: 0.381 AC: 15805 AN: 41488

American (AMR) AF: 0.278 AC: 4241 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3462

East Asian (EAS) AF: 0.428 AC: 2210 AN: 5160

South Asian (SAS) AF: 0.220 AC: 1065 AN: 4830

European-Finnish (FIN) AF: 0.275 AC: 2906 AN: 10576

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14132 AN: 67950

Other (OTH) AF: 0.240 AC: 506 AN: 2104

Alfa AF: 0.226 Hom.: 11118

Bravo AF: 0.280

Asia WGS AF: 0.381 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.6
DANN	Benign	0.70
PhyloP100		-0.24
PromoterAI		-0.012	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6489721; hg19: chr12-6643316;