NM_024757.5:c.1089T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

Kleefstra syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Kleefstra syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

EHMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 65724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
EHMT1	NM_024757.5 link	c.1089T>C	p.Gly363Gly	synonymous_variant	Exon 6 of 27	ENST00000460843.6	NP_079033.4	Q9H9B1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6 link	c.1089T>C	p.Gly363Gly	synonymous_variant	Exon 6 of 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

GnomAD2 exomes

AF:

0.395

AC:

99134

AN:

251076

AF XY:

0.382

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 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

African (AFR)

AF:

0.817

AC:

27353

AN:

33480

American (AMR)

AF:

0.567

AC:

25339

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

11394

AN:

26136

East Asian (EAS)

AF:

0.131

AC:

5209

AN:

39700

South Asian (SAS)

AF:

0.367

AC:

31653

AN:

86254

European-Finnish (FIN)

AF:

0.282

AC:

15011

AN:

53324

Middle Eastern (MID)

AF:

0.440

AC:

2538

AN:

5768

European-Non Finnish (NFE)

AF:

0.353

AC:

392464

AN:

1111996

Other (OTH)

AF:

0.382

AC:

23062

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

20877

41754

62630

83507

104384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12656

25312

37968

50624

63280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.487

AC:

74016

AN:

152080

Hom.:

21318

Cov.:

AF XY:

0.482

AC XY:

35861

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.797

AC:

33095

AN:

41502

American (AMR)

AF:

0.536

AC:

8194

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1491

AN:

3468

East Asian (EAS)

AF:

0.124

AC:

640

AN:

5164

South Asian (SAS)

AF:

0.357

AC:

1723

AN:

4824

European-Finnish (FIN)

AF:

0.283

AC:

2995

AN:

10566

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24368

AN:

67962

Other (OTH)

AF:

0.476

AC:

1002

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1671

3341

5012

6682

8353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.402

Hom.:

7050

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

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 25, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kleefstra syndrome 1

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 18, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 11, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.35

PhyloP100

-1.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over