rs11882238

Positions:

• chr19-35540496-C-A
• chr19-35540496-C-G
• chr19-35540496-C-T

Variant summary

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

The NM_014364.5(GAPDHS):​c.449+1813C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,920 control chromosomes in the GnomAD database, including 10,505 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 0.36 (10505 hom., cov: 31)
• Consequence: GAPDHS NM_014364.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPDHS	NM_014364.5	c.449+1813C>A		intron_variant		ENST00000222286.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPDHS	ENST00000222286.9	c.449+1813C>A		intron_variant		1	NM_014364.5	P1
GAPDHS	ENST00000585510.1	c.245+1813C>A		intron_variant		3
GAPDHS	ENST00000586334.1	c.*136+1813C>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55198 AN: 151802 Hom.: 10494 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.364 AC: 55238 AN: 151920 Hom.: 10505 Cov.: 31 AF XY: 0.369 AC XY: 27399 AN XY: 74250

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.330

Alfa AF: 0.354 Hom.: 20299

Bravo AF: 0.361

Asia WGS AF: 0.512 AC: 1782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.83

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: rs11882238; hg19: chr19-36031398;