12-6535530-T-A

Variant names:

• chr12-6535530-T-A
• rs1060621
• NM_002046.7:c.29+669T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002046.7(GAPDH):​c.29+669T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 692,454 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GAPDH NM_002046.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDH	NM_002046.7	MANE Select	c.29+669T>A		intron	N/A	NP_002037.2
	GAPDH	NM_001289745.3		c.29+669T>A		intron	N/A	NP_001276674.1
	GAPDH	NM_001289746.2		c.29+669T>A		intron	N/A	NP_001276675.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDH	ENST00000229239.10	TSL:1 MANE Select	c.29+669T>A		intron	N/A	ENSP00000229239.5
	GAPDH	ENST00000396859.5	TSL:1	c.29+669T>A		intron	N/A	ENSP00000380068.1
	GAPDH	ENST00000396861.5	TSL:5	c.29+669T>A		intron	N/A	ENSP00000380070.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 1 AN: 692454 Hom.: 0 AF XY: 0.00000310 AC XY: 1 AN XY: 322226

African (AFR) AF: 0.00 AC: 0 AN: 12998

American (AMR) AF: 0.00 AC: 0 AN: 838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4262

East Asian (EAS) AF: 0.00 AC: 0 AN: 2946

South Asian (SAS) AF: 0.00 AC: 0 AN: 13828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1360

European-Non Finnish (NFE) AF: 0.00000158 AC: 1 AN: 633366

Other (OTH) AF: 0.00 AC: 0 AN: 22592

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		-0.027
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1060621; hg19: chr12-6644696;