NM_001242699.2:c.533T>G

Variant names:

• chr10-116859037-T-G
• rs759636926
• NM_001242699.2:c.533T>G

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.533T>G​(p.Leu178Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L178S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• 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=0.19547242).

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.533T>G	p.Leu178Trp	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.533T>G	p.Leu178Trp	missense	Exon 4 of 14	ENSP00000345555.6	A6NNW6-3
	ENO4	ENST00000409522.5	TSL:1	c.165+9306T>G		intron	N/A	ENSP00000387194.1	A6NNW6-2
	ENO4	ENST00000369207.3	TSL:5	c.2T>G	p.Leu1?	start_lost	Exon 1 of 11	ENSP00000358208.2	A0A5H1ZRQ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383504 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 682684

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35710

South Asian (SAS) AF: 0.00 AC: 0 AN: 79194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078692

Other (OTH) AF: 0.00 AC: 0 AN: 57892

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Benign	0.96
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.75	T
PhyloP100		2.0
PrimateAI	Uncertain	0.52	T
REVEL	Benign	0.29
Sift4G	Uncertain	0.0070	D
Vest4		0.40
MVP		0.35
ClinPred		0.26	T
GERP RS		4.1
PromoterAI		-0.0036	Neutral
Varity_R		0.081
gMVP		0.44
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: rs759636926; hg19: chr10-118618548;