9-137817430-A-C

Variant names:

• chr9-137817430-A-C
• rs73578877
• ENST00000475564.5:n.1090A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000475564.5(EHMT1):​n.1090A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,613,274 control chromosomes in the GnomAD database, including 10,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (5310 hom., cov: 33)
  • Exomes 𝑓: 0.016 (4788 hom.)
• Consequence: EHMT1 ENST00000475564.5 non_coding_transcript_exon
• Scores: Splicing: ADA: 0.000005028
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0360
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-137817430-A-C is Benign according to our data. Variant chr9-137817430-A-C is described in ClinVar as Benign. ClinVar VariationId is 96155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475564.5. 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.3375-9A>C		intron	N/A	NP_079033.4
	EHMT1	NM_001354263.2		c.3354-9A>C		intron	N/A	NP_001341192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT1	ENST00000475564.5	TSL:1	n.1090A>C		non_coding_transcript_exon	Exon 1 of 4
	EHMT1	ENST00000460843.6	TSL:5 MANE Select	c.3375-9A>C		intron	N/A	ENSP00000417980.1
	EHMT1	ENST00000494249.5	TSL:1	n.728-9A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22099 AN: 151380 Hom.: 5291 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00169

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.0393 AC: 9864 AN: 250958 AF XY: 0.0290

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.0301

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00319

Gnomad OTH exome AF: 0.0256

GnomAD4 exome AF: 0.0162 AC: 23719 AN: 1461776 Hom.: 4788 Cov.: 31 AF XY: 0.0141 AC XY: 10257 AN XY: 727194

African (AFR) AF: 0.517 AC: 17322 AN: 33474

American (AMR) AF: 0.0338 AC: 1511 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 48 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00101 AC: 87 AN: 86256

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53370

Middle Eastern (MID) AF: 0.0387 AC: 223 AN: 5768

European-Non Finnish (NFE) AF: 0.00212 AC: 2354 AN: 1111954

Other (OTH) AF: 0.0359 AC: 2168 AN: 60394

GnomAD4 genome AF: 0.146 AC: 22161 AN: 151498 Hom.: 5310 Cov.: 33 AF XY: 0.141 AC XY: 10406 AN XY: 74002

African (AFR) AF: 0.500 AC: 20653 AN: 41332

American (AMR) AF: 0.0662 AC: 1008 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00148 AC: 7 AN: 4738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10516

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00337 AC: 228 AN: 67746

Other (OTH) AF: 0.115 AC: 241 AN: 2100

Alfa AF: 0.0518 Hom.: 702

Bravo AF: 0.167

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

Jul 02, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Kleefstra syndrome 1 Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.48
PhyloP100		0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000050
dbscSNV1_RF	Benign	0.0040
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: rs73578877; hg19: chr9-140711882;