rs373269573

Positions:

chr9-137711015-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_024757.5(EHMT1):c.70G>A(p.Glu24Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000235 in 1,594,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

EHMT1
NM_024757.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:5

Conservation

PhyloP100: 4.47

Variant links:

Genes affected

EHMT1 (HGNC:24650): (euchromatic histone lysine methyltransferase 1) The protein encoded by this gene is a histone methyltransferase that methylates the lysine-9 position of histone H3. This action marks the genomic region packaged with these methylated histones for transcriptional repression. This protein may be involved in the silencing of MYC- and E2F-responsive genes and therefore could play a role in the G0/G1 cell cycle transition. Defects in this gene are a cause of chromosome 9q subtelomeric deletion syndrome (9q-syndrome, also known as Kleefstra syndrome). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

EHMT1 links:

EHMT1 (HGNC:):

EHMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16409111).

BP6

Variant 9-137711015-G-A is Benign according to our data. Variant chr9-137711015-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195380.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2, Benign=2}.

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHMT1	NM_024757.5 linkuse as main transcript	c.70G>A	p.Glu24Lys	missense_variant	2/27	ENST00000460843.6	NP_079033.4	Q9H9B1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6 linkuse as main transcript	c.70G>A	p.Glu24Lys	missense_variant	2/27	5	NM_024757.5	ENSP00000417980.1		Q9H9B1-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

212862

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

115346

show subpopulations

Gnomad AFR exome

AF:

0.000164

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000633

Gnomad SAS exome

AF:

0.0000382

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000253

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000250

AC:

361

AN:

1441822

Hom.:

Cov.:

AF XY:

0.000262

AC XY:

187

AN XY:

715022

show subpopulations

Gnomad4 AFR exome

AF:

0.0000904

Gnomad4 AMR exome

AF:

0.000167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000306

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000279

AC:

ExAC

AF:

0.000125

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Kleefstra syndrome 1

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Oct 24, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 12, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 07, 2016

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2019

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

EHMT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 26, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.69

N;N;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.61

N;N;.;.

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D;.;.

Sift4G

Benign

0.11

T;T;.;D

Polyphen

0.92

P;P;.;.

Vest4

0.56

MVP

0.44

MPC

0.15

ClinPred

0.13

GERP RS

4.1

Varity_R

0.26

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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