9-137839709-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000462942.3(EHMT1):c.2398-6851T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,014 control chromosomes in the GnomAD database, including 19,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19881 hom., cov: 32)
• Consequence: EHMT1 ENST00000462942.3 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT1	ENST00000462942.3	c.2398-6851T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76566 AN: 151898 Hom.: 19852 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.495

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.504 AC: 76650 AN: 152014 Hom.: 19881 Cov.: 32 AF XY: 0.508 AC XY: 37734 AN XY: 74312

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.499

Alfa AF: 0.465 Hom.: 27398

Bravo AF: 0.497

Asia WGS AF: 0.691 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.6
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4526432; hg19: chr9-140734161;