12-6535556-A-G

Variant names:

• chr12-6535556-A-G
• rs1060620
• NM_002046.7:c.29+695A>G

Variant summary

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

The NM_002046.7(GAPDH):​c.29+695A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 610,906 control chromosomes in the GnomAD database, including 21,377 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 (9272 hom., cov: 32)
  • Exomes 𝑓: 0.23 (12105 hom.)
• Consequence: GAPDH NM_002046.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 11 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002046.7. 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
	GAPDH	NM_002046.7	MANE Select	c.29+695A>G		intron	N/A	NP_002037.2
	GAPDH	NM_001289745.3		c.29+695A>G		intron	N/A	NP_001276674.1
	GAPDH	NM_001289746.2		c.29+695A>G		intron	N/A	NP_001276675.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDH	ENST00000229239.10	TSL:1 MANE Select	c.29+695A>G		intron	N/A	ENSP00000229239.5
	GAPDH	ENST00000396859.5	TSL:1	c.29+695A>G		intron	N/A	ENSP00000380068.1
	GAPDH	ENST00000396861.5	TSL:5	c.29+695A>G		intron	N/A	ENSP00000380070.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48546 AN: 151894 Hom.: 9242 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.226 AC: 103657 AN: 458894 Hom.: 12105 AF XY: 0.224 AC XY: 48141 AN XY: 214908

African (AFR) AF: 0.531 AC: 4544 AN: 8564

American (AMR) AF: 0.280 AC: 150 AN: 536

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 490 AN: 2792

East Asian (EAS) AF: 0.507 AC: 984 AN: 1940

South Asian (SAS) AF: 0.256 AC: 2345 AN: 9174

European-Finnish (FIN) AF: 0.244 AC: 43 AN: 176

Middle Eastern (MID) AF: 0.134 AC: 121 AN: 906

European-Non Finnish (NFE) AF: 0.217 AC: 91147 AN: 419830

Other (OTH) AF: 0.256 AC: 3833 AN: 14976

GnomAD4 genome AF: 0.320 AC: 48624 AN: 152012 Hom.: 9272 Cov.: 32 AF XY: 0.322 AC XY: 23901 AN XY: 74300

African (AFR) AF: 0.522 AC: 21650 AN: 41456

American (AMR) AF: 0.297 AC: 4539 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2524 AN: 5176

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4824

European-Finnish (FIN) AF: 0.277 AC: 2924 AN: 10552

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14237 AN: 67948

Other (OTH) AF: 0.277 AC: 584 AN: 2110

Alfa AF: 0.249 Hom.: 2045

Bravo AF: 0.331

Asia WGS AF: 0.429 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.9
DANN	Benign	0.67
PhyloP100		0.15
PromoterAI		-0.026	Neutral
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: rs1060620; hg19: chr12-6644722;