NM_006709.5:c.3060G>T

Variant names:

• chr6-31882944-C-A
• NM_006709.5:c.3060G>T
• EHMT2 p.Ala1020Ala

Variant summary

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

The NM_006709.5(EHMT2):​c.3060G>T​(p.Ala1020Ala) 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. A1020A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EHMT2 NM_006709.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.66
• Publications: 0 publications found

Genes affected

EHMT2 (HGNC:14129): (euchromatic histone lysine methyltransferase 2) This gene encodes a methyltransferase that methylates lysine residues of histone H3. Methylation of H3 at lysine 9 by this protein results in recruitment of additional epigenetic regulators and repression of transcription. This gene was initially thought to be two different genes, NG36 and G9a, adjacent to each other in the HLA locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

EHMT2-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

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=-0.71).
• BP7: Synonymous conserved (PhyloP=-4.66 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006709.5. 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
	EHMT2	NM_006709.5	MANE Select	c.3060G>T	p.Ala1020Ala	synonymous	Exon 24 of 28	NP_006700.3
	EHMT2	NM_001363689.2		c.3231G>T	p.Ala1077Ala	synonymous	Exon 23 of 27	NP_001350618.1	A2ABF9
	EHMT2	NM_001289413.2		c.3129G>T	p.Ala1043Ala	synonymous	Exon 22 of 26	NP_001276342.1	A2ABF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2	ENST00000375537.9	TSL:1 MANE Select	c.3060G>T	p.Ala1020Ala	synonymous	Exon 24 of 28	ENSP00000364687.4	Q96KQ7-1
	EHMT2	ENST00000395728.7	TSL:1	c.3231G>T	p.Ala1077Ala	synonymous	Exon 23 of 27	ENSP00000379078.3	A2ABF9
	EHMT2	ENST00000962959.1		c.3060G>T	p.Ala1020Ala	synonymous	Exon 24 of 29	ENSP00000633018.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.98
DANN	Benign	0.83
PhyloP100		-4.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-31850721;