chr10-116881577-C-A

Variant names:

• chr10-116881577-C-A
• rs2133286684
• NM_001242699.2:c.1786C>A

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.1786C>A​(p.Leu596Ile) 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. 16/20 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. L596F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• 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]

SHTN1 (HGNC:29319): (shootin 1) Enables identical protein binding activity. Involved in positive regulation of neuron migration. Located in cytoplasm. [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=0.06962225).

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.1786C>A	p.Leu596Ile	missense	Exon 14 of 14	NP_001229628.1	A6NNW6-3
	SHTN1	NM_001127211.3	MANE Select	c.*4767G>T		3_prime_UTR	Exon 17 of 17	NP_001120683.1	A0MZ66-1
	SHTN1	NM_001258298.2		c.*4767G>T		3_prime_UTR	Exon 16 of 16	NP_001245227.1	A0MZ66-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO4	ENST00000341276.11	TSL:5 MANE Select	c.1786C>A	p.Leu596Ile	missense	Exon 14 of 14	ENSP00000345555.6	A6NNW6-3
	ENO4	ENST00000409522.5	TSL:1	c.835C>A	p.Leu279Ile	missense	Exon 7 of 7	ENSP00000387194.1	A6NNW6-2
	SHTN1	ENST00000355371.9	TSL:2 MANE Select	c.*4767G>T		3_prime_UTR	Exon 17 of 17	ENSP00000347532.4	A0MZ66-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.77
DANN	Benign	0.78
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.11
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.071
Sift	Benign	0.40	T
Sift4G	Benign	0.50	T
Polyphen		0.28	B
Vest4		0.20
MVP		0.088
ClinPred		0.12	T
GERP RS		2.5
Varity_R		0.037
gMVP		0.12
Mutation Taster		=99/1	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: rs2133286684; hg19: chr10-118641088;