Genetic Variant EZHIP:p.Gly111Gly (chrX-51407349-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_203407.3(EZHIP):c.333G>T(p.Gly111Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 567,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 72 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., 33 hem., cov: 23)

Exomes 𝑓: 0.00025 ( 0 hom. 39 hem. )

Consequence

EZHIP
NM_203407.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.965

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-51407349-G-T is Benign according to our data. Variant chrX-51407349-G-T is described in ClinVar as [Benign]. Clinvar id is 737121.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.965 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZHIP	NM_203407.3 link	c.333G>T	p.Gly111Gly	synonymous_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.333G>T	p.Gly111Gly	synonymous_variant	Exon 1 of 1	6	NM_203407.3	ENSP00000342680.2		Q86X51
ENSG00000226530	ENST00000455931.2 link	n.757+10668G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.000712

AC:

AN:

112372

Hom.:

Cov.:

AF XY:

0.000956

AC XY:

AN XY:

34532

show subpopulations

Gnomad AFR

AF:

0.000129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000508

AC:

AN:

173177

Hom.:

AF XY:

0.000527

AC XY:

AN XY:

60729

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00320

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:

0.00

Gnomad OTH exome

AF:

0.000466

GnomAD4 exome

AF:

0.000251

AC:

114

AN:

454791

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

AN XY:

168829

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00327

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:

0.00

Gnomad4 OTH exome

AF:

0.0000806

GnomAD4 genome

AF:

0.000712

AC:

AN:

112424

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

34594

show subpopulations

Gnomad4 AFR

AF:

0.000129

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000850

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.38

DANN

Benign

0.57

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