rs112664025

Variant names:

• chr9-137817423-ACT-A
• rs112664025
• ENST00000475564.5:n.1088_1089delCT

Variant summary

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

The ENST00000475564.5(EHMT1):​n.1088_1089delCT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 1,613,552 control chromosomes in the GnomAD database, including 3,276 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (241 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3035 hom.)
• Consequence: EHMT1 ENST00000475564.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0480
• Publications: 0 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 9-137817423-ACT-A is Benign according to our data. Variant chr9-137817423-ACT-A is described in ClinVar as Benign. ClinVar VariationId is 96154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT1	NM_024757.5	c.3375-11_3375-10delCT		intron_variant	Intron 23 of 26	ENST00000460843.6	NP_079033.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6	c.3375-11_3375-10delCT		intron_variant	Intron 23 of 26	5	NM_024757.5	ENSP00000417980.1

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7821 AN: 151730 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0588

Gnomad OTH AF: 0.0489

GnomAD2 exomes AF: 0.0549 AC: 13758 AN: 250808 AF XY: 0.0594

Gnomad AFR exome AF: 0.0488

Gnomad AMR exome AF: 0.0221

Gnomad ASJ exome AF: 0.0338

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.0469

Gnomad NFE exome AF: 0.0606

Gnomad OTH exome AF: 0.0498

GnomAD4 exome AF: 0.0596 AC: 87168 AN: 1461704 Hom.: 3035 AF XY: 0.0617 AC XY: 44884 AN XY: 727178

African (AFR) AF: 0.0451 AC: 1511 AN: 33478

American (AMR) AF: 0.0226 AC: 1013 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0339 AC: 886 AN: 26134

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39700

South Asian (SAS) AF: 0.119 AC: 10239 AN: 86254

European-Finnish (FIN) AF: 0.0466 AC: 2483 AN: 53336

Middle Eastern (MID) AF: 0.0426 AC: 246 AN: 5768

European-Non Finnish (NFE) AF: 0.0605 AC: 67318 AN: 1111920

Other (OTH) AF: 0.0573 AC: 3459 AN: 60390

GnomAD4 genome AF: 0.0516 AC: 7840 AN: 151848 Hom.: 241 Cov.: 32 AF XY: 0.0514 AC XY: 3813 AN XY: 74194

African (AFR) AF: 0.0483 AC: 1999 AN: 41416

American (AMR) AF: 0.0306 AC: 467 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3468

East Asian (EAS) AF: 0.00175 AC: 9 AN: 5146

South Asian (SAS) AF: 0.120 AC: 576 AN: 4800

European-Finnish (FIN) AF: 0.0436 AC: 459 AN: 10536

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0588 AC: 3990 AN: 67902

Other (OTH) AF: 0.0512 AC: 108 AN: 2108

Alfa AF: 0.0508 Hom.: 43

Bravo AF: 0.0484

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Nov 26, 2013

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:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 09, 2019

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		0.048
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs112664025; hg19: chr9-140711875;