rs1129767

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024757.5(EHMT1):c.1044G>A(p.Ser348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,684 control chromosomes in the GnomAD database, including 28,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2436 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26387 hom. )

Consequence

EHMT1
NM_024757.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-137743964-G-A is Benign according to our data. Variant chr9-137743964-G-A is described in ClinVar as [Benign]. Clinvar id is 65723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137743964-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHMT1	NM_024757.5 linkuse as main transcript	c.1044G>A	p.Ser348=	synonymous_variant	6/27	ENST00000460843.6	NP_079033.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6 linkuse as main transcript	c.1044G>A	p.Ser348=	synonymous_variant	6/27	5	NM_024757.5	ENSP00000417980		Q9H9B1-1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23203

AN:

152148

Hom.:

2428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0335

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.203

AC:

50848

AN:

250544

Hom.:

6878

AF XY:

0.198

AC XY:

26846

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.0305

Gnomad AMR exome

AF:

0.434

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.0963

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.181

AC:

264306

AN:

1461418

Hom.:

26387

Cov.:

AF XY:

0.183

AC XY:

132775

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.0276

Gnomad4 AMR exome

AF:

0.420

Gnomad4 ASJ exome

AF:

0.206

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.153

AC:

23224

AN:

152266

Hom.:

2436

Cov.:

AF XY:

0.157

AC XY:

11683

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0334

Gnomad4 AMR

AF:

0.308

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.164

Hom.:

1483

Bravo

AF:

0.157

Asia WGS

AF:

0.135

AC:

471

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 25, 2014	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Kleefstra syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.28

DANN

Benign

0.76

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

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