rs10780183

Positions:

• chr9-137700463-A-G
• chr9-137700463-A-T

Variant summary

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

The NM_024757.5(EHMT1):​c.22-10504A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,216 control chromosomes in the GnomAD database, including 2,722 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 0.18 (2722 hom., cov: 32)
• Consequence: EHMT1 NM_024757.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHMT1	NM_024757.5	c.22-10504A>G		intron_variant		ENST00000460843.6	NP_079033.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6	c.22-10504A>G		intron_variant		5	NM_024757.5	ENSP00000417980

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27388 AN: 152098 Hom.: 2713 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.180 AC: 27422 AN: 152216 Hom.: 2722 Cov.: 32 AF XY: 0.185 AC XY: 13746 AN XY: 74410

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.164

Alfa AF: 0.171 Hom.: 1298

Bravo AF: 0.187

Asia WGS AF: 0.157 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.26

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

Other links and lift over

dbSNP: rs10780183; hg19: chr9-140594915;