rs781890238

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-51407881-G-A
• chrX-51407881-G-C
• chrX-51407881-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_203407.3(EZHIP):​c.865G>A​(p.Ala289Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 555,525 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 5 hem., cov: 24)
  • Exomes 𝑓: 0.00014 (0 hom. 17 hem.)
• Consequence: EZHIP NM_203407.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04451242).
• BP6: Variant X-51407881-G-A is Benign according to our data. Variant chrX-51407881-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2660567.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 5 gene

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>A	p.Ala289Thr	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>A	p.Ala289Thr	missense	Exon 1 of 1	ENSP00000342680.2	Q86X51
	ENSG00000226530	ENST00000455931.2	TSL:3	n.757+11200G>A		intron	N/A
	ENSG00000226530	ENST00000767703.1		n.736+11200G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 13 AN: 112234 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00427

Gnomad NFE AF: 0.000208

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000114 AC: 17 AN: 149614 AF XY: 0.000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000767

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000172

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000140 AC: 62 AN: 443244 Hom.: 0 Cov.: 0 AF XY: 0.000105 AC XY: 17 AN XY: 162442

African (AFR) AF: 0.00 AC: 0 AN: 13768

American (AMR) AF: 0.00 AC: 0 AN: 33677

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15175

East Asian (EAS) AF: 0.00 AC: 0 AN: 26689

South Asian (SAS) AF: 0.000195 AC: 8 AN: 41040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33618

Middle Eastern (MID) AF: 0.000333 AC: 1 AN: 3000

European-Non Finnish (NFE) AF: 0.000202 AC: 51 AN: 251860

Other (OTH) AF: 0.0000819 AC: 2 AN: 24417

GnomAD4 genome AF: 0.000116 AC: 13 AN: 112281 Hom.: 0 Cov.: 24 AF XY: 0.000145 AC XY: 5 AN XY: 34467

African (AFR) AF: 0.00 AC: 0 AN: 31000

American (AMR) AF: 0.00 AC: 0 AN: 10772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3496

South Asian (SAS) AF: 0.000371 AC: 1 AN: 2697

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6238

Middle Eastern (MID) AF: 0.00469 AC: 1 AN: 213

European-Non Finnish (NFE) AF: 0.000208 AC: 11 AN: 52995

Other (OTH) AF: 0.00 AC: 0 AN: 1536

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.000121 AC: 14

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.034	T
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.033
Sift	Benign	0.23	T
Sift4G	Uncertain	0.040	D
Polyphen		0.22	B
Vest4		0.021
MVP		0.36
MPC		0.11
ClinPred		0.049	T
GERP RS		-2.0
Varity_R		0.11
gMVP		0.16
Mutation Taster		=94/6	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;