8-109336150-C-G

Variant names:

• chr8-109336150-C-G
• rs750806375
• NM_020189.6:c.29C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020189.6(ENY2):​c.29C>G​(p.Ala10Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,070 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ENY2 NM_020189.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78
• Publications: 4 publications found

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]

ACMG classification

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=0.1524443).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENY2	NM_020189.6	MANE Select	c.29C>G	p.Ala10Gly	missense	Exon 2 of 5	NP_064574.1	Q9NPA8-1
	ENY2	NM_001193557.2		c.14C>G	p.Ala5Gly	missense	Exon 2 of 5	NP_001180486.1	Q9NPA8-2
	ENY2	NR_036471.2		n.151C>G		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENY2	ENST00000521688.6	TSL:1 MANE Select	c.29C>G	p.Ala10Gly	missense	Exon 2 of 5	ENSP00000429986.1	Q9NPA8-1
	ENY2	ENST00000517350.5	TSL:1	n.1770C>G		non_coding_transcript_exon	Exon 1 of 4
	ENY2	ENST00000520147.5	TSL:4	c.14C>G	p.Ala5Gly	missense	Exon 2 of 6	ENSP00000429588.1	E5RHX8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248470 AF XY: 0.00

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: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461070 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726824

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0026	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.089
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.060
Sift	Benign	0.36	T
Sift4G	Benign	0.38	T
Polyphen		0.11	B
Vest4		0.32
MutPred		0.27		Gain of methylation at K8 (P = 0.1312)
MVP		0.28
MPC		1.1
ClinPred		0.41	T
GERP RS		5.5
Varity_R		0.38
gMVP		0.39
Mutation Taster		=45/55	disease causing

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: rs750806375; hg19: chr8-110348379;