chrX-51407881-G-C

Variant names:

• chrX-51407881-G-C
• rs781890238
• NM_203407.3:c.865G>C

Variant summary

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

The NM_203407.3(EZHIP):​c.865G>C​(p.Ala289Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 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. A289T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 24)
• Consequence: EZHIP NM_203407.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 1 publications found

Genes affected

EZHIP (HGNC:33738): (EZH inhibitory protein) Involved in negative regulation of histone H3-K27 methylation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000226530 (HGNC:):

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=0.17473784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203407.3. 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
	EZHIP	NM_203407.3	MANE Select	c.865G>C	p.Ala289Pro	missense	Exon 1 of 1	NP_981952.1	Q86X51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EZHIP	ENST00000342995.4	TSL:6 MANE Select	c.865G>C	p.Ala289Pro	missense	Exon 1 of 1	ENSP00000342680.2	Q86X51
	ENSG00000226530	ENST00000455931.2	TSL:3	n.757+11200G>C		intron	N/A
	ENSG00000226530	ENST00000767703.1		n.736+11200G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.033	T
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.93	T
PhyloP100		2.3
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.25	T
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.14
MutPred		0.18		Gain of glycosylation at A289 (P = 0.0273)
MVP		0.63
MPC		0.19
ClinPred		0.39	T
GERP RS		-2.0
Varity_R		0.20
gMVP		0.28
Mutation Taster		=81/19	polymorphism

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: rs781890238; hg19: chrX-51150733;