rs750806375

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-109336150-C-G
• chr8-109336150-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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

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=0.1524443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENY2	NM_020189.6	c.29C>G	p.Ala10Gly	missense_variant	Exon 2 of 5	ENST00000521688.6	NP_064574.1
ENY2	NM_001193557.2	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 5		NP_001180486.1
ENY2	NR_036471.2	n.151C>G		non_coding_transcript_exon_variant	Exon 2 of 5
ENY2	NR_036472.2	n.151C>G		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENY2	ENST00000521688.6	c.29C>G	p.Ala10Gly	missense_variant	Exon 2 of 5	1	NM_020189.6	ENSP00000429986.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248470 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134880

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.060
Sift	Benign	0.36	T;T;T
Sift4G	Benign	0.38	T;T;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

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

Other links and lift over

dbSNP: rs750806375; hg19: chr8-110348379;