8-109336150-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12904721).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENY2NM_020189.6 linkc.29C>T p.Ala10Val missense_variant Exon 2 of 5 ENST00000521688.6 NP_064574.1 Q9NPA8-1A0A024R9D9
ENY2NM_001193557.2 linkc.14C>T p.Ala5Val missense_variant Exon 2 of 5 NP_001180486.1 Q9NPA8-2
ENY2NR_036471.2 linkn.151C>T non_coding_transcript_exon_variant Exon 2 of 5
ENY2NR_036472.2 linkn.151C>T non_coding_transcript_exon_variant Exon 2 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENY2ENST00000521688.6 linkc.29C>T p.Ala10Val missense_variant Exon 2 of 5 1 NM_020189.6 ENSP00000429986.1 Q9NPA8-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152006
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248470
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134880
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 SAS 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:
26
AN:
1461066
Hom.:
0
Cov.:
30
AF XY:
0.0000179
AC XY:
13
AN XY:
726820
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152006
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74240
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.29C>T (p.A10V) alteration is located in exon 2 (coding exon 2) of the ENY2 gene. This alteration results from a C to T substitution at nucleotide position 29, causing the alanine (A) at amino acid position 10 to be replaced by a valine (V). 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
0.14
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.030
.;T;.
Eigen
Benign
0.024
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.2
.;L;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.59
N;N;N
REVEL
Benign
0.059
Sift
Benign
0.33
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.0040
.;B;.
Vest4
0.34
MutPred
0.37
.;Gain of catalytic residue at A10 (P = 0.0313);.;
MVP
0.27
MPC
0.91
ClinPred
0.20
T
GERP RS
5.5
Varity_R
0.32
gMVP
0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs750806375; hg19: chr8-110348379; COSMIC: COSV53455799; COSMIC: COSV53455799; API