chr10-116856586-C-T

Variant names:

• chr10-116856586-C-T
• rs200907862
• NM_001242699.2:c.389C>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.389C>T​(p.Ala130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,383,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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. A130T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02
• Publications: 0 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=0.14513654).

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.389C>T	p.Ala130Val	missense	Exon 3 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.389C>T	p.Ala130Val	missense	Exon 3 of 14	ENSP00000345555.6	A6NNW6-3
	ENO4	ENST00000409522.5	TSL:1	c.165+6855C>T		intron	N/A	ENSP00000387194.1	A6NNW6-2
	ENO4	ENST00000969696.1		c.260C>T	p.Ala87Val	missense	Exon 2 of 12	ENSP00000639755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000730 AC: 1 AN: 137044 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000304 AC: 42 AN: 1383838 Hom.: 0 Cov.: 30 AF XY: 0.0000293 AC XY: 20 AN XY: 682860

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000840 AC: 3 AN: 35734

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.0000352 AC: 38 AN: 1078886

Other (OTH) AF: 0.00 AC: 0 AN: 57914

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000416 AC: 1

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	0.13
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.0060
Eigen_PC	Benign	-0.081
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.94	T
PhyloP100		2.0
PrimateAI	Benign	0.40	T
REVEL	Benign	0.12
Sift4G	Uncertain	0.014	D
Vest4		0.23
MVP		0.040
ClinPred		0.71	D
GERP RS		4.0
Varity_R		0.054
gMVP		0.54
Mutation Taster		=89/11	polymorphism

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: rs200907862; hg19: chr10-118616097; COSMIC: COSV58004353; COSMIC: COSV58004353;