Genetic Variant EZHIP:p.Ser30Thr (chrX-51407104-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_203407.3(EZHIP):c.88T>A(p.Ser30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 568,746 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 76 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., 10 hem., cov: 24)

Exomes 𝑓: 0.00035 ( 0 hom. 66 hem. )

Consequence

EZHIP
NM_203407.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0780

Variant links:

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]

EZHIP links:

ENSG00000226530 (HGNC:):

ENSG00000226530 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015537411).

BP6

Variant X-51407104-T-A is Benign according to our data. Variant chrX-51407104-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660565.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZHIP	NM_203407.3 link	c.88T>A	p.Ser30Thr	missense_variant	Exon 1 of 1	ENST00000342995.4	NP_981952.1	Q86X51A0A515VFR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EZHIP	ENST00000342995.4 link	c.88T>A	p.Ser30Thr	missense_variant	Exon 1 of 1	6	NM_203407.3	ENSP00000342680.2		Q86X51
ENSG00000226530	ENST00000455931.2 link	n.757+10423T>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.000295

AC:

AN:

111682

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

33866

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

Gnomad ASJ

AF:

0.00340

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000396

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000310

AC:

AN:

180788

Hom.:

AF XY:

0.000351

AC XY:

AN XY:

65616

show subpopulations

Gnomad AFR exome

AF:

0.0000771

Gnomad AMR exome

AF:

0.000293

Gnomad ASJ exome

AF:

0.00242

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000536

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.000346

AC:

158

AN:

457015

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

AN XY:

170777

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000175

Gnomad4 ASJ exome

AF:

0.00208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000381

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000363

Gnomad4 OTH exome

AF:

0.000361

GnomAD4 genome

AF:

0.000286

AC:

AN:

111731

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

33925

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00340

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000396

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000738

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000313

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EZHIP: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.037

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.28

M_CAP

Benign

0.0084

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

PROVEAN

Benign

-1.5

REVEL

Benign

0.079

Sift

Benign

0.43

Sift4G

Benign

0.31

Polyphen

0.94

Vest4

0.083

MVP

0.29

MPC

0.25

ClinPred

0.029

GERP RS

-1.2

Varity_R

0.089

gMVP

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over