rs397792796

Variant names:

• chr9-137834335-T-TTC
• rs10667884
• NM_024757.5:c.3541-11_3541-10dupTC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_024757.5(EHMT1):​c.3541-11_3541-10dupTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,612,306 control chromosomes in the GnomAD database, including 18,014 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4782 hom., cov: 30)
  • Exomes 𝑓: 0.11 (13232 hom.)
• Consequence: EHMT1 NM_024757.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.314
• Publications: 2 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 9-137834335-T-TTC is Benign according to our data. Variant chr9-137834335-T-TTC is described in ClinVar as Benign. ClinVar VariationId is 96157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT1	NM_024757.5	c.3541-11_3541-10dupTC		intron_variant	Intron 25 of 26	ENST00000460843.6	NP_079033.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6	c.3541-11_3541-10dupTC		intron_variant	Intron 25 of 26	5	NM_024757.5	ENSP00000417980.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30918 AN: 152088 Hom.: 4752 Cov.: 30

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.147 AC: 36202 AN: 246224 AF XY: 0.132

Gnomad AFR exome AF: 0.436

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.0826

Gnomad EAS exome AF: 0.0107

Gnomad FIN exome AF: 0.0619

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.115 AC: 167532 AN: 1460102 Hom.: 13232 Cov.: 31 AF XY: 0.112 AC XY: 81495 AN XY: 726456

African (AFR) AF: 0.447 AC: 14948 AN: 33454

American (AMR) AF: 0.332 AC: 14803 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 2182 AN: 26090

East Asian (EAS) AF: 0.00917 AC: 364 AN: 39686

South Asian (SAS) AF: 0.0978 AC: 8431 AN: 86250

European-Finnish (FIN) AF: 0.0663 AC: 3462 AN: 52228

Middle Eastern (MID) AF: 0.114 AC: 655 AN: 5766

European-Non Finnish (NFE) AF: 0.104 AC: 115175 AN: 1111630

Other (OTH) AF: 0.124 AC: 7512 AN: 60348

GnomAD4 genome AF: 0.204 AC: 31012 AN: 152204 Hom.: 4782 Cov.: 30 AF XY: 0.199 AC XY: 14808 AN XY: 74432

African (AFR) AF: 0.431 AC: 17883 AN: 41490

American (AMR) AF: 0.246 AC: 3757 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 294 AN: 3468

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5184

South Asian (SAS) AF: 0.101 AC: 489 AN: 4830

European-Finnish (FIN) AF: 0.0644 AC: 684 AN: 10620

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7327 AN: 67994

Other (OTH) AF: 0.183 AC: 387 AN: 2114

Alfa AF: 0.149 Hom.: 434

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Sep 25, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kleefstra syndrome 1 Benign:2

Aug 17, 2021

Fulgent Genetics, Fulgent Genetics

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:1

Mar 26, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10667884; hg19: chr9-140728787; COSMIC: COSV107502334; COSMIC: COSV107502334;