19-35534023-G-C

Variant names:

• chr19-35534023-G-C
• rs4806173
• NM_014364.5:c.67+429G>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.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
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDHS	NM_014364.5	MANE Select	c.67+429G>C		intron	N/A	NP_055179.1	O14556

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDHS	ENST00000222286.9	TSL:1 MANE Select	c.67+429G>C		intron	N/A	ENSP00000222286.3	O14556
	GAPDHS	ENST00000586334.1	TSL:2	n.67+429G>C		intron	N/A	ENSP00000466432.1	K7EMB2

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

African (AFR) AF: 0.678 AC: 28127 AN: 41478

American (AMR) AF: 0.660 AC: 10094 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3470

East Asian (EAS) AF: 0.754 AC: 3900 AN: 5170

South Asian (SAS) AF: 0.708 AC: 3419 AN: 4826

European-Finnish (FIN) AF: 0.679 AC: 7203 AN: 10616

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

European-Non Finnish (NFE) AF: 0.613 AC: 41688 AN: 67970

Other (OTH) AF: 0.602 AC: 1274 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.41
PhyloP100		0.23
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: rs4806173; hg19: chr19-36024925;