rs776780490

Variant names:

• chr9-137834788-G-A
• rs776780490
• NM_024757.5:c.3732G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-137834788-G-A
• chr9-137834788-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_024757.5(EHMT1):​c.3732G>A​(p.Glu1244Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EHMT1 NM_024757.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0490
• Publications: 1 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 9-137834788-G-A is Benign according to our data. Variant chr9-137834788-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1100535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.049 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT1	NM_024757.5	MANE Select	c.3732G>A	p.Glu1244Glu	synonymous	Exon 27 of 27	NP_079033.4
	EHMT1	NM_001354263.2		c.3711G>A	p.Glu1237Glu	synonymous	Exon 27 of 27	NP_001341192.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT1	ENST00000460843.6	TSL:5 MANE Select	c.3732G>A	p.Glu1244Glu	synonymous	Exon 27 of 27	ENSP00000417980.1	Q9H9B1-1
	EHMT1	ENST00000475564.5	TSL:1	n.1456G>A		non_coding_transcript_exon	Exon 4 of 4
	EHMT1	ENST00000494249.5	TSL:1	n.1085G>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248548 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Kleefstra syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.0
DANN	Benign	0.88
PhyloP100		-0.049

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: rs776780490; hg19: chr9-140729240;