chr19-35538950-T-C

Variant names:

• chr19-35538950-T-C
• rs12984928
• NM_014364.5:c.449+267T>C

Variant summary

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

The NM_014364.5(GAPDHS):​c.449+267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,008 control chromosomes in the GnomAD database, including 28,444 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 0.61 (28444 hom., cov: 32)
• Consequence: GAPDHS NM_014364.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 5 publications found

Genes affected

GAPDHS (HGNC:24864): (glyceraldehyde-3-phosphate dehydrogenase, spermatogenic) This gene encodes a protein belonging to the glyceraldehyde-3-phosphate dehydrogenase family of enzymes that play an important role in carbohydrate metabolism. Like its somatic cell counterpart, this sperm-specific enzyme functions in a nicotinamide adenine dinucleotide-dependent manner to remove hydrogen and add phosphate to glyceraldehyde 3-phosphate to form 1,3-diphosphoglycerate. During spermiogenesis, this enzyme may play an important role in regulating the switch between different energy-producing pathways, and it is required for sperm motility and male fertility. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAPDHS	NM_014364.5	c.449+267T>C		intron_variant	Intron 4 of 10	ENST00000222286.9	NP_055179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAPDHS	ENST00000222286.9	c.449+267T>C		intron_variant	Intron 4 of 10	1	NM_014364.5	ENSP00000222286.3
GAPDHS	ENST00000585510.1	c.245+267T>C		intron_variant	Intron 3 of 5	3		ENSP00000467255.1
GAPDHS	ENST00000586334.1	n.*136+267T>C		intron_variant	Intron 3 of 5	2		ENSP00000466432.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92363 AN: 151890 Hom.: 28411 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.583

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.608 AC: 92436 AN: 152008 Hom.: 28444 Cov.: 32 AF XY: 0.613 AC XY: 45507 AN XY: 74272

African (AFR) AF: 0.554 AC: 22944 AN: 41426

American (AMR) AF: 0.642 AC: 9812 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3470

East Asian (EAS) AF: 0.754 AC: 3901 AN: 5172

South Asian (SAS) AF: 0.709 AC: 3414 AN: 4814

European-Finnish (FIN) AF: 0.679 AC: 7189 AN: 10580

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41562 AN: 67964

Other (OTH) AF: 0.578 AC: 1218 AN: 2106

Alfa AF: 0.595 Hom.: 3396

Bravo AF: 0.603

Asia WGS AF: 0.664 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		-0.57
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: rs12984928; hg19: chr19-36029852;