NM_024757.5:c.22-3774G>A

Variant names:

• chr9-137707193-G-A
• rs4634736
• NM_024757.5:c.22-3774G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024757.5(EHMT1):​c.22-3774G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,256 control chromosomes in the GnomAD database, including 836 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 0.10 (836 hom., cov: 33)
• Consequence: EHMT1 NM_024757.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 10 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)

ENSG00000283411 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT1	NM_024757.5	c.22-3774G>A		intron_variant	Intron 1 of 26	ENST00000460843.6	NP_079033.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6	c.22-3774G>A		intron_variant	Intron 1 of 26	5	NM_024757.5	ENSP00000417980.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15313 AN: 152138 Hom.: 837 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.101 AC: 15320 AN: 152256 Hom.: 836 Cov.: 33 AF XY: 0.0977 AC XY: 7273 AN XY: 74444

African (AFR) AF: 0.131 AC: 5431 AN: 41538

American (AMR) AF: 0.0839 AC: 1283 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3470

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5186

South Asian (SAS) AF: 0.0700 AC: 338 AN: 4832

European-Finnish (FIN) AF: 0.0419 AC: 444 AN: 10596

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6956 AN: 68016

Other (OTH) AF: 0.108 AC: 228 AN: 2114

Alfa AF: 0.101 Hom.: 1063

Bravo AF: 0.104

Asia WGS AF: 0.0400 AC: 143 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	2.5
DANN	Benign	0.53
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4634736; hg19: chr9-140601645;