chr10-116849716-C-A

Variant names:

• chr10-116849716-C-A
• rs772187861
• NM_001242699.2:c.150C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001242699.2(ENO4):​c.150C>A​(p.Asp50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,529,216 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: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.238
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30997926).

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.150C>A	p.Asp50Glu	missense	Exon 1 of 14	NP_001229628.1	A6NNW6-3
	HSPA12A	NM_001330164.2		c.-148G>T		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.150C>A	p.Asp50Glu	missense	Exon 1 of 14	ENSP00000345555.6	A6NNW6-3
	ENO4	ENST00000409522.5	TSL:1	c.150C>A	p.Asp50Glu	missense	Exon 1 of 7	ENSP00000387194.1	A6NNW6-2
	ENO4	ENST00000969696.1		c.150C>A	p.Asp50Glu	missense	Exon 1 of 12	ENSP00000639755.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000628 AC: 8 AN: 127486 AF XY: 0.0000441

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000909

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000109 AC: 150 AN: 1377008 Hom.: 0 Cov.: 30 AF XY: 0.0000960 AC XY: 65 AN XY: 676920

African (AFR) AF: 0.00 AC: 0 AN: 31066

American (AMR) AF: 0.0000594 AC: 2 AN: 33652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23676

East Asian (EAS) AF: 0.00 AC: 0 AN: 35222

South Asian (SAS) AF: 0.00 AC: 0 AN: 75686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4958

European-Non Finnish (NFE) AF: 0.000137 AC: 146 AN: 1068298

Other (OTH) AF: 0.0000352 AC: 2 AN: 56874

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.000458 AC: 7 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000493 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.24
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.87	N
REVEL	Uncertain	0.49
Sift	Benign	0.067	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.57		Gain of helix (P = 0.0225)
MVP		0.48
ClinPred		0.40	T
GERP RS		0.52
PromoterAI		-0.038	Neutral
Varity_R		0.24
gMVP		0.66
Mutation Taster		=77/23	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: rs772187861; hg19: chr10-118609227;