10-116859000-G-T

Variant names:

• chr10-116859000-G-T
• rs368025714
• NM_001242699.2:c.496G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242699.2(ENO4):​c.496G>T​(p.Ala166Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000261 in 1,532,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign 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. A166T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14795655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242699.2. 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
	ENO4	NM_001242699.2	MANE Select	c.496G>T	p.Ala166Ser	missense	Exon 4 of 14	NP_001229628.1	A6NNW6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO4	ENST00000341276.11	TSL:5 MANE Select	c.496G>T	p.Ala166Ser	missense	Exon 4 of 14	ENSP00000345555.6	A6NNW6-3
	ENO4	ENST00000409522.5	TSL:1	c.165+9269G>T		intron	N/A	ENSP00000387194.1	A6NNW6-2
	ENO4	ENST00000969696.1		c.367G>T	p.Ala123Ser	missense	Exon 3 of 12	ENSP00000639755.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151988 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000734 AC: 1 AN: 136160 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000415

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1380910 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 681526

African (AFR) AF: 0.00 AC: 0 AN: 31534

American (AMR) AF: 0.0000281 AC: 1 AN: 35546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 35638

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077012

Other (OTH) AF: 0.00 AC: 0 AN: 57794

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151988 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74220

African (AFR) AF: 0.0000483 AC: 2 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.75
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
PhyloP100		4.2
PrimateAI	Benign	0.29	T
REVEL	Benign	0.11
Sift4G	Benign	0.62	T
Vest4		0.14
MVP		0.081
ClinPred		0.23	T
GERP RS		5.3
PromoterAI		-0.0054	Neutral
Varity_R		0.10
gMVP		0.16
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs368025714; hg19: chr10-118618511;