NM_014364.5:c.263G>C

Variant names:

• chr19-35538324-G-C
• NM_014364.5:c.263G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014364.5(GAPDHS):​c.263G>C​(p.Arg88Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GAPDHS NM_014364.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.95

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAPDHS	NM_014364.5	c.263G>C	p.Arg88Pro	missense_variant	Exon 3 of 11	ENST00000222286.9	NP_055179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAPDHS	ENST00000222286.9	c.263G>C	p.Arg88Pro	missense_variant	Exon 3 of 11	1	NM_014364.5	ENSP00000222286.3
GAPDHS	ENST00000585510.1	c.59G>C	p.Arg20Pro	missense_variant	Exon 2 of 6	3		ENSP00000467255.1
GAPDHS	ENST00000586334.1	n.85G>C		non_coding_transcript_exon_variant	Exon 2 of 6	2		ENSP00000466432.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Uncertain	0.029	D
MutationAssessor	Pathogenic	3.9	H;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.7	D;.
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.014	D;D
Polyphen		1.0	D;.
Vest4		0.97
MutPred		0.83		Loss of MoRF binding (P = 0.0034);.;
MVP		0.86
MPC		0.75
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.99
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36029226;