12-6535530-T-G

Variant names:

• chr12-6535530-T-G
• rs1060621
• NM_002046.7:c.29+669T>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+669T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 842,918 control chromosomes in the GnomAD database, including 16,801 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 0.19 (3039 hom., cov: 33)
  • Exomes 𝑓: 0.20 (13762 hom.)
• Consequence: GAPDH NM_002046.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 8 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAPDH	NM_002046.7	c.29+669T>G		intron_variant	Intron 2 of 8	ENST00000229239.10	NP_002037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAPDH	ENST00000229239.10	c.29+669T>G		intron_variant	Intron 2 of 8	1	NM_002046.7	ENSP00000229239.5

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29563 AN: 152020 Hom.: 3035 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.197 AC: 136399 AN: 690780 Hom.: 13762 AF XY: 0.197 AC XY: 63168 AN XY: 321422

African (AFR) AF: 0.167 AC: 2167 AN: 12972

American (AMR) AF: 0.210 AC: 176 AN: 838

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 464 AN: 4252

East Asian (EAS) AF: 0.382 AC: 1124 AN: 2940

South Asian (SAS) AF: 0.123 AC: 1705 AN: 13812

European-Finnish (FIN) AF: 0.155 AC: 41 AN: 264

Middle Eastern (MID) AF: 0.0935 AC: 127 AN: 1358

European-Non Finnish (NFE) AF: 0.200 AC: 126162 AN: 631800

Other (OTH) AF: 0.197 AC: 4433 AN: 22544

GnomAD4 genome AF: 0.194 AC: 29576 AN: 152138 Hom.: 3039 Cov.: 33 AF XY: 0.194 AC XY: 14405 AN XY: 74400

African (AFR) AF: 0.177 AC: 7337 AN: 41488

American (AMR) AF: 0.212 AC: 3238 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3466

East Asian (EAS) AF: 0.367 AC: 1896 AN: 5162

South Asian (SAS) AF: 0.125 AC: 605 AN: 4830

European-Finnish (FIN) AF: 0.209 AC: 2215 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13335 AN: 67976

Other (OTH) AF: 0.173 AC: 366 AN: 2112

Alfa AF: 0.192 Hom.: 598

Bravo AF: 0.196

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		-0.027
PromoterAI		-0.0084	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1060621; hg19: chr12-6644696;