rs137852717

Variant names:

• chr9-137776636-C-A
• NM_024757.5:c.1810C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-137776636-C-A
• chr9-137776636-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024757.5(EHMT1):​c.1810C>A​(p.Gln604Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EHMT1 NM_024757.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.91

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]

ENSG00000255585 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28584233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT1	NM_024757.5	c.1810C>A	p.Gln604Lys	missense_variant	Exon 12 of 27	ENST00000460843.6	NP_079033.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6	c.1810C>A	p.Gln604Lys	missense_variant	Exon 12 of 27	5	NM_024757.5	ENSP00000417980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;.;T;.;.;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.8	L;L;.;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N;N;.;.;.;.
REVEL	Benign	0.12
Sift	Benign	0.26	T;T;.;.;.;.
Sift4G	Benign	0.42	T;T;.;.;.;T
Polyphen		0.15	B;D;.;.;.;.
Vest4		0.61
MutPred		0.38		Gain of methylation at Q604 (P = 0.0017);Gain of methylation at Q604 (P = 0.0017);.;.;.;.;
MVP		0.72
MPC		1.0
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.36
gMVP		0.86

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140671088;