rs3812497

Variant names:

Variant summary

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

The NM_024757.5(EHMT1):c.444T>C(p.Pro148Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,608,838 control chromosomes in the GnomAD database, including 62,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5098 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57545 hom. )

Consequence

EHMT1
NM_024757.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.319

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=-0.54).

BP6

Variant 9-137716984-T-C is Benign according to our data. Variant chr9-137716984-T-C is described in ClinVar as [Benign]. Clinvar id is 65738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137716984-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.319 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT1	NM_024757.5 link	c.444T>C	p.Pro148Pro	synonymous_variant	Exon 3 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.444T>C	p.Pro148Pro	synonymous_variant	Exon 3 of 27	5	NM_024757.5	ENSP00000417980.1		Q9H9B1-1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36622

AN:

152002

Hom.:

5091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.288

AC:

72036

AN:

249932

Hom.:

11921

AF XY:

0.287

AC XY:

38869

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.277

GnomAD4 exome

AF:

0.275

AC:

400861

AN:

1456718

Hom.:

57545

Cov.:

AF XY:

0.277

AC XY:

200831

AN XY:

723724

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.471

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.241

AC:

36649

AN:

152120

Hom.:

5098

Cov.:

AF XY:

0.244

AC XY:

18112

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.275

Hom.:

7116

Bravo

AF:

0.244

Asia WGS

AF:

0.190

AC:

665

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

May 23, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kleefstra syndrome 1

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 05, 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

-0.54

CADD

Benign

6.2

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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