NM_014364.5:c.800C>T

Variant names:

• chr19-35543398-C-T
• NM_014364.5:c.800C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014364.5(GAPDHS):​c.800C>T​(p.Ala267Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A267S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GAPDHS NM_014364.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38
• Publications: 0 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]

TMEM147-AS1 (HGNC:51273): (TMEM147 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38859695).

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.800C>T	p.Ala267Val	missense	Exon 8 of 11	NP_055179.1	O14556
	TMEM147-AS1	NR_038396.1		n.94-125G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDHS	ENST00000222286.9	TSL:1 MANE Select	c.800C>T	p.Ala267Val	missense	Exon 8 of 11	ENSP00000222286.3	O14556
	TMEM147-AS1	ENST00000590717.2	TSL:1	n.2110G>A		non_coding_transcript_exon	Exon 1 of 3
	TMEM147-AS1	ENST00000589137.5	TSL:1	n.94-125G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.098
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.096
Sift	Benign	0.11	T
Sift4G	Benign	0.18	T
Polyphen		0.88	P
Vest4		0.53
MutPred		0.55		Gain of methylation at K266 (P = 0.0411)
MVP		0.52
MPC		0.26
ClinPred		0.29	T
GERP RS		1.7
Varity_R		0.096
gMVP		0.67
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr19-36034300;