rs779277999

Variant names:

• chr9-137800888-A-C
• rs779277999
• NM_024757.5:c.2616A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137800888-A-C
• chr9-137800888-A-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024757.5(EHMT1):​c.2616A>C​(p.Gly872Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G872G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EHMT1 NM_024757.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.29
• Publications: 0 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: 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=-0.87).
• BP7: Synonymous conserved (PhyloP=-4.29 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT1	NM_024757.5	MANE Select	c.2616A>C	p.Gly872Gly	synonymous	Exon 18 of 27	NP_079033.4
	EHMT1	NM_001354263.2		c.2595A>C	p.Gly865Gly	synonymous	Exon 18 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.2616A>C	p.Gly872Gly	synonymous	Exon 18 of 27	ENSP00000417980.1
	EHMT1	ENST00000637161.1	TSL:5	c.2523A>C	p.Gly841Gly	synonymous	Exon 18 of 27	ENSP00000490328.1
	EHMT1	ENST00000636027.1	TSL:5	c.2502A>C	p.Gly834Gly	synonymous	Exon 18 of 21	ENSP00000489961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.52
PhyloP100		-4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs779277999; hg19: chr9-140695340;