chr12-6535090-T-A

Variant names:

• chr12-6535090-T-A
• rs3741918
• NM_002046.7:c.29+229T>A

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+229T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 759,242 control chromosomes in the GnomAD database, including 16,848 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 0.22 (3655 hom., cov: 33)
  • Exomes 𝑓: 0.20 (13193 hom.)
• Consequence: GAPDH NM_002046.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDH	NM_002046.7	MANE Select	c.29+229T>A		intron	N/A	NP_002037.2
	GAPDH	NM_001289745.3		c.29+229T>A		intron	N/A	NP_001276674.1
	GAPDH	NM_001289746.2		c.29+229T>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+229T>A		intron	N/A	ENSP00000229239.5
	GAPDH	ENST00000396859.5	TSL:1	c.29+229T>A		intron	N/A	ENSP00000380068.1
	GAPDH	ENST00000496049.1	TSL:2	n.339T>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32704 AN: 152024 Hom.: 3649 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.201 AC: 122172 AN: 607098 Hom.: 13193 Cov.: 8 AF XY: 0.197 AC XY: 60628 AN XY: 308154

African (AFR) AF: 0.218 AC: 2649 AN: 12162

American (AMR) AF: 0.217 AC: 2910 AN: 13390

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 1225 AN: 13288

East Asian (EAS) AF: 0.312 AC: 8050 AN: 25784

South Asian (SAS) AF: 0.119 AC: 5144 AN: 43102

European-Finnish (FIN) AF: 0.230 AC: 6400 AN: 27818

Middle Eastern (MID) AF: 0.0908 AC: 209 AN: 2302

European-Non Finnish (NFE) AF: 0.204 AC: 89585 AN: 439028

Other (OTH) AF: 0.199 AC: 6000 AN: 30224

GnomAD4 genome AF: 0.215 AC: 32725 AN: 152144 Hom.: 3655 Cov.: 33 AF XY: 0.213 AC XY: 15868 AN XY: 74390

African (AFR) AF: 0.225 AC: 9327 AN: 41532

American (AMR) AF: 0.217 AC: 3327 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0877 AC: 304 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1940 AN: 5156

South Asian (SAS) AF: 0.125 AC: 601 AN: 4826

European-Finnish (FIN) AF: 0.228 AC: 2423 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14186 AN: 67944

Other (OTH) AF: 0.189 AC: 399 AN: 2108

Alfa AF: 0.213 Hom.: 449

Bravo AF: 0.218

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.58
PhyloP100		-0.66
PromoterAI		-0.071	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: rs3741918; hg19: chr12-6644256;