6-31896770-G-T

Variant names:

• chr6-31896770-G-T
• rs7887
• NM_006709.5:c.164C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006709.5(EHMT2):​c.164C>A​(p.Thr55Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,612,788 control chromosomes in the GnomAD database, including 103,389 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.30 (8483 hom., cov: 32)
  • Exomes 𝑓: 0.35 (94906 hom.)
• Consequence: EHMT2 NM_006709.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5850968E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT2	NM_006709.5	c.164C>A	p.Thr55Asn	missense_variant	Exon 3 of 28	ENST00000375537.9	NP_006700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT2	ENST00000375537.9	c.164C>A	p.Thr55Asn	missense_variant	Exon 3 of 28	1	NM_006709.5	ENSP00000364687.4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45038 AN: 152018 Hom.: 8470 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.395 AC: 96900 AN: 245270 Hom.: 21436 AF XY: 0.391 AC XY: 52263 AN XY: 133836

Gnomad AFR exome AF: 0.0691

Gnomad AMR exome AF: 0.592

Gnomad ASJ exome AF: 0.514

Gnomad EAS exome AF: 0.558

Gnomad SAS exome AF: 0.333

Gnomad FIN exome AF: 0.351

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.349 AC: 510309 AN: 1460650 Hom.: 94906 Cov.: 55 AF XY: 0.351 AC XY: 255068 AN XY: 726648

Gnomad4 AFR exome AF: 0.0632

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.296 AC: 45057 AN: 152138 Hom.: 8483 Cov.: 32 AF XY: 0.301 AC XY: 22418 AN XY: 74358

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.302

Alfa AF: 0.338 Hom.: 9194

Bravo AF: 0.298

TwinsUK AF: 0.343 AC: 1270

ALSPAC AF: 0.323 AC: 1246

ESP6500AA AF: 0.0927 AC: 280

ESP6500EA AF: 0.348 AC: 1888

ExAC AF: 0.382 AC: 44783

Asia WGS AF: 0.377 AC: 1315 AN: 3478

EpiCase AF: 0.378

EpiControl AF: 0.388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.40
DANN	Benign	0.49
DEOGEN2	Benign	0.025	.;.;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.051	N
MetaRNN	Benign	0.000046	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.72	N;N;N;N
REVEL	Benign	0.057
Sift	Benign	1.0	T;T;T;T
Sift4G	Uncertain	0.047	D;D;D;D
Polyphen		0.0	.;B;B;B
Vest4		0.0070
MPC		0.56
ClinPred		0.0039	T
GERP RS		-6.0
Varity_R		0.031
gMVP		0.052

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

LitVar

Other links and lift over

dbSNP: rs7887; hg19: chr6-31864547; COSMIC: COSV64994251; COSMIC: COSV64994251;