rs112664025

Positions:

• chr9-137817423-ACT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_024757.5(EHMT1):​c.3375-11_3375-10del variant causes a splice polypyrimidine tract, intron 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 NM_024757.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0480

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 96154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137817423-ACT-A is described in Lovd as [Likely_benign].
• 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/exons	MANE	UniProt
EHMT1	NM_024757.5	c.3375-11_3375-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000460843.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT1	ENST00000460843.6	c.3375-11_3375-10del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_024757.5

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

GnomAD3 exomes AF: 0.0549 AC: 13758 AN: 250808 Hom.: 530 AF XY: 0.0594 AC XY: 8064 AN XY: 135654

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 SAS exome AF: 0.120

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

Gnomad4 AFR exome AF: 0.0451

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0339

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0466

Gnomad4 NFE exome AF: 0.0605

Gnomad4 OTH exome AF: 0.0573

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

Gnomad4 AFR AF: 0.0483

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0436

Gnomad4 NFE AF: 0.0588

Gnomad4 OTH AF: 0.0512

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 26, 2013	- -

Kleefstra syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs112664025; hg19: chr9-140711875;