NM_001242699.2:c.152T>C

Variant names:

• chr10-116849718-T-C
• NM_001242699.2:c.152T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001242699.2(ENO4):​c.152T>C​(p.Val51Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000073 in 1,370,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46
• 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]

HSPA12A (HGNC:19022): (heat shock protein family A (Hsp70) member 12A) Predicted to enable ATP binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28684127).

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.152T>C	p.Val51Ala	missense	Exon 1 of 14	NP_001229628.1	A6NNW6-3
	HSPA12A	NM_001330164.2		c.-150A>G		5_prime_UTR	Exon 1 of 13	NP_001317093.1	A0A1B0GTF3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO4	ENST00000341276.11	TSL:5 MANE Select	c.152T>C	p.Val51Ala	missense	Exon 1 of 14	ENSP00000345555.6	A6NNW6-3
	ENO4	ENST00000409522.5	TSL:1	c.152T>C	p.Val51Ala	missense	Exon 1 of 7	ENSP00000387194.1	A6NNW6-2
	ENO4	ENST00000969696.1		c.152T>C	p.Val51Ala	missense	Exon 1 of 12	ENSP00000639755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1370444 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 673594

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30788

American (AMR) AF: 0.00 AC: 0 AN: 33038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23542

East Asian (EAS) AF: 0.00 AC: 0 AN: 34726

South Asian (SAS) AF: 0.00 AC: 0 AN: 74820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4910

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1064690

Other (OTH) AF: 0.00 AC: 0 AN: 56542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	Uncertain	0.45
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.27
Sift	Uncertain	0.014	D
Sift4G	Benign	0.32	T
Polyphen		0.88	P
Vest4		0.24
MutPred		0.49		Loss of helix (P = 0.0626)
MVP		0.35
ClinPred		0.92	D
GERP RS		4.7
PromoterAI		-0.0070	Neutral
Varity_R		0.12
gMVP		0.41
Mutation Taster		=70/30	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

hg19: chr10-118609229;