rs11137244

Variant names:

• chr9-137813437-G-A
• rs11137244
• NM_024757.5:c.3087G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-137813437-G-A
• chr9-137813437-G-C
• chr9-137813437-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024757.5(EHMT1):​c.3087G>A​(p.Val1029Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00957 in 1,613,706 control chromosomes in the GnomAD database, including 963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (486 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (477 hom.)
• Consequence: EHMT1 NM_024757.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.11
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 9-137813437-G-A is Benign according to our data. Variant chr9-137813437-G-A is described in ClinVar as Benign. ClinVar VariationId is 128979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024757.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT1	NM_024757.5	MANE Select	c.3087G>A	p.Val1029Val	synonymous	Exon 21 of 27	NP_079033.4
	EHMT1	NM_001354263.2		c.3066G>A	p.Val1022Val	synonymous	Exon 21 of 27	NP_001341192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT1	ENST00000460843.6	TSL:5 MANE Select	c.3087G>A	p.Val1029Val	synonymous	Exon 21 of 27	ENSP00000417980.1
	EHMT1	ENST00000637161.1	TSL:5	c.2994G>A	p.Val998Val	synonymous	Exon 21 of 27	ENSP00000490328.1
	EHMT1	ENST00000462942.3	TSL:2	n.1944G>A		non_coding_transcript_exon	Exon 16 of 22	ENSP00000436107.1

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6793 AN: 152134 Hom.: 486 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.0344

GnomAD2 exomes AF: 0.0128 AC: 3212 AN: 250336 AF XY: 0.00981

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000187

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00591 AC: 8637 AN: 1461454 Hom.: 477 Cov.: 33 AF XY: 0.00535 AC XY: 3886 AN XY: 727016

African (AFR) AF: 0.159 AC: 5320 AN: 33474

American (AMR) AF: 0.0136 AC: 608 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000476 AC: 41 AN: 86188

European-Finnish (FIN) AF: 0.0000940 AC: 5 AN: 53202

Middle Eastern (MID) AF: 0.0258 AC: 149 AN: 5768

European-Non Finnish (NFE) AF: 0.00150 AC: 1671 AN: 1111922

Other (OTH) AF: 0.0138 AC: 835 AN: 60386

GnomAD4 genome AF: 0.0447 AC: 6801 AN: 152252 Hom.: 486 Cov.: 33 AF XY: 0.0434 AC XY: 3234 AN XY: 74440

African (AFR) AF: 0.148 AC: 6155 AN: 41506

American (AMR) AF: 0.0266 AC: 407 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00226 AC: 154 AN: 68020

Other (OTH) AF: 0.0340 AC: 72 AN: 2116

Alfa AF: 0.0187 Hom.: 275

Bravo AF: 0.0513

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.00360

EpiControl AF: 0.00255

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Kleefstra syndrome 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.8
DANN	Benign	0.54
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=87/13	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: rs11137244; hg19: chr9-140707889;