10-116860859-G-T

Variant names:

• chr10-116860859-G-T
• rs1846390265
• NM_001242699.2:c.700G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001242699.2(ENO4):​c.700G>T​(p.Gly234Cys) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G234S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02

Genes affected

ENO4 (HGNC:31670): (enolase 4) Predicted to enable phosphopyruvate hydratase activity. Predicted to be involved in glycolytic process and regulation of vacuole fusion, non-autophagic. Predicted to act upstream of or within cilium organization and flagellated sperm motility. Predicted to be located in sperm principal piece. Predicted to be part of phosphopyruvate hydratase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO4	NM_001242699.2	c.700G>T	p.Gly234Cys	missense_variant	Exon 5 of 14	ENST00000341276.11	NP_001229628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO4	ENST00000341276.11	c.700G>T	p.Gly234Cys	missense_variant	Exon 5 of 14	5	NM_001242699.2	ENSP00000345555.6
ENO4	ENST00000409522.5	c.166-7791G>T		intron_variant	Intron 1 of 6	1		ENSP00000387194.1
ENO4	ENST00000622726.4	c.703G>T	p.Gly235Cys	missense_variant	Exon 6 of 16	5
ENO4	ENST00000369207.3	c.169G>T	p.Gly57Cys	missense_variant	Exon 2 of 11	5		ENSP00000358208.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;.
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Uncertain	0.33	D
PrimateAI	Uncertain	0.50	T
REVEL	Pathogenic	0.82
Sift4G	Pathogenic	0.0	D;D
Vest4		0.90
MVP		0.43
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.58
gMVP		0.79

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: rs1846390265; hg19: chr10-118620370;