dbSNP rs750806375: ENY2:p.Ala10Val (chr8-109336150-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020189.6(ENY2):c.29C>T(p.Ala10Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ENY2
NM_020189.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

Publications

4 publications found

Variant links:

Genes affected

ENY2 (HGNC:24449): (ENY2 transcription and export complex 2 subunit) Enables nuclear receptor coactivator activity. Involved in histone deubiquitination; poly(A)+ mRNA export from nucleus; and positive regulation of transcription, DNA-templated. Located in mitochondrion and nucleoplasm. Part of nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENY2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.12904721).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020189.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENY2	NM_020189.6	MANE Select	c.29C>T	p.Ala10Val	missense	Exon 2 of 5	NP_064574.1	Q9NPA8-1
ENY2	NM_001193557.2		c.14C>T	p.Ala5Val	missense	Exon 2 of 5	NP_001180486.1	Q9NPA8-2
ENY2	NR_036471.2		n.151C>T		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENY2	ENST00000521688.6	TSL:1 MANE Select	c.29C>T	p.Ala10Val	missense	Exon 2 of 5	ENSP00000429986.1	Q9NPA8-1
ENY2	ENST00000517350.5	TSL:1	n.1770C>T		non_coding_transcript_exon	Exon 1 of 4
ENY2	ENST00000520147.5	TSL:4	c.14C>T	p.Ala5Val	missense	Exon 2 of 6	ENSP00000429588.1	E5RHX8

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

248470

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461066

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726820

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33452

American (AMR)

AF:

0.0000671

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111492

Other (OTH)

AF:

0.0000497

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

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:

0.0000329

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41364

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

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

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

Eigen

Benign

0.024

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

M_CAP

Benign

0.0033

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

PhyloP100

4.8

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.59

REVEL

Benign

0.059

Sift

Benign

0.33

Sift4G

Benign

0.34

Polyphen

0.0040

Vest4

0.34

MutPred

0.37

Gain of catalytic residue at A10 (P = 0.0313)

MVP

0.27

MPC

0.91

ClinPred

0.20

GERP RS

5.5

Varity_R

0.32

gMVP

0.50

Mutation Taster

=43/57

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over