9-137744009-T-C

Position:

chr9-137744009-T-C

Variant summary

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

The NM_024757.5(EHMT1):c.1089T>C(p.Gly363Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,613,856 control chromosomes in the GnomAD database, including 125,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 21318 hom., cov: 33)

Exomes 𝑓: 0.37 ( 104256 hom. )

Consequence

EHMT1
NM_024757.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.02

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 9-137744009-T-C is Benign according to our data. Variant chr9-137744009-T-C is described in ClinVar as [Benign]. Clinvar id is 65724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137744009-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 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.1089T>C	p.Gly363Gly	synonymous_variant	6/27	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.1089T>C	p.Gly363Gly	synonymous_variant	6/27	5	NM_024757.5	ENSP00000417980.1		Q9H9B1-1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73917

AN:

151962

Hom.:

21278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.797

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.481

GnomAD3 exomes

AF:

0.395

AC:

99134

AN:

251076

Hom.:

22862

AF XY:

0.382

AC XY:

51845

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.805

Gnomad AMR exome

AF:

0.572

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.365

AC:

534023

AN:

1461776

Hom.:

104256

Cov.:

AF XY:

0.365

AC XY:

265084

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.817

Gnomad4 AMR exome

AF:

0.567

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.367

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.487

AC:

74016

AN:

152080

Hom.:

21318

Cov.:

AF XY:

0.482

AC XY:

35861

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.797

Gnomad4 AMR

AF:

0.536

Gnomad4 ASJ

AF:

0.430

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.400

Hom.:

4633

Bravo

AF:

0.519

Asia WGS

AF:

0.251

AC:

877

AN:

3478

EpiCase

AF:

0.371

EpiControl

AF:

0.362

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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	Eurofins Ntd Llc (ga)	Sep 25, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Kleefstra syndrome 1

Benign:2

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

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 18, 2018	- -

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

-0.92

CADD

Benign

0.086

DANN

Benign

0.35

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

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