Genetic Variant NM_001242699.2:c.65A>G (chr10-116849631-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001242699.2(ENO4):c.65A>G(p.Gln22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,550,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ENO4
NM_001242699.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Publications

0 publications found

Variant links:

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]

ENO4 links:

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]

HSPA12A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033574104).

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.65A>G	p.Gln22Arg	missense	Exon 1 of 14	NP_001229628.1	A6NNW6-3
	HSPA12A	NM_001330164.2		c.-63T>C		5_prime_UTR	Exon 1 of 13	NP_001317093.1	A0A1B0GTF3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENO4	ENST00000341276.11	TSL:5 MANE Select	c.65A>G	p.Gln22Arg	missense	Exon 1 of 14	ENSP00000345555.6	A6NNW6-3
ENO4	ENST00000409522.5	TSL:1	c.65A>G	p.Gln22Arg	missense	Exon 1 of 7	ENSP00000387194.1	A6NNW6-2
ENO4	ENST00000969696.1		c.65A>G	p.Gln22Arg	missense	Exon 1 of 12	ENSP00000639755.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000410

AC:

AN:

146228

AF XY:

0.0000761

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000557

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1397910

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

689482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31592

American (AMR)

AF:

0.00

AC:

AN:

35668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25162

East Asian (EAS)

AF:

0.00

AC:

AN:

35696

South Asian (SAS)

AF:

0.000114

AC:

AN:

79190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000742

AC:

AN:

1078786

Other (OTH)

AF:

0.0000173

AC:

AN:

57964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000476

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0060

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.68

M_CAP

Benign

0.063

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.35

PhyloP100

2.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.2

REVEL

Benign

0.074

Sift

Benign

0.43

Sift4G

Benign

0.14

Polyphen

0.0010

Vest4

0.32

MutPred

0.19

Gain of MoRF binding (P = 0.0181)

MVP

0.21

ClinPred

0.090

GERP RS

3.6

PromoterAI

0.037

Neutral

(source)

Varity_R

0.076

gMVP

0.21

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over