10-116871142-G-T

Variant names:

• chr10-116871142-G-T
• NM_001242699.2:c.1065G>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.1065G>T​(p.Lys355Asn) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87

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=0.16807812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO4	NM_001242699.2	c.1065G>T	p.Lys355Asn	missense_variant	Exon 9 of 14	ENST00000341276.11	NP_001229628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO4	ENST00000341276.11	c.1065G>T	p.Lys355Asn	missense_variant	Exon 9 of 14	5	NM_001242699.2	ENSP00000345555.6
ENO4	ENST00000409522.5	c.240G>T	p.Lys80Asn	missense_variant	Exon 3 of 7	1		ENSP00000387194.1
ENO4	ENST00000622726.4	c.1074G>T	p.Lys358Asn	missense_variant	Exon 11 of 16	5
ENO4	ENST00000369207.3	c.534G>T	p.Lys178Asn	missense_variant	Exon 6 of 11	5		ENSP00000358208.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1065G>T (p.K355N) alteration is located in exon 9 (coding exon 9) of the ENO4 gene. This alteration results from a G to T substitution at nucleotide position 1065, causing the lysine (K) at amino acid position 355 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.096
Eigen_PC	Benign	0.097
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.83	T;T;.;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.030	N;.;.;N
REVEL	Benign	0.10
Sift	Uncertain	0.014	D;.;.;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.020	B;.;.;.
Vest4		0.19
MVP		0.32
ClinPred		0.84	D
GERP RS		5.1
Varity_R		0.093
gMVP		0.31
Mutation Taster		=94/6	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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-118630653;