19-35534023-G-C

Position:

• chr19-35534023-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014364.5(GAPDHS):​c.67+429G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,148 control chromosomes in the GnomAD database, including 31,903 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 0.65 (31903 hom., cov: 33)
• Consequence: GAPDHS NM_014364.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAPDHS	NM_014364.5	c.67+429G>C		intron_variant		ENST00000222286.9	NP_055179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAPDHS	ENST00000222286.9	c.67+429G>C		intron_variant		1	NM_014364.5	ENSP00000222286.3
GAPDHS	ENST00000586334.1	n.67+429G>C		intron_variant		2		ENSP00000466432.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98063 AN: 152030 Hom.: 31869 Cov.: 33

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.645 AC: 98143 AN: 152148 Hom.: 31903 Cov.: 33 AF XY: 0.649 AC XY: 48293 AN XY: 74390

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.602

Alfa AF: 0.623 Hom.: 3702

Bravo AF: 0.645

Asia WGS AF: 0.672 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs4806173; hg19: chr19-36024925;