Genetic Variant SUV39H1:p.Thr260Thr (chrX-48700705-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003173.4(SUV39H1):c.780C>T(p.Thr260Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,209,952 control chromosomes in the GnomAD database, including 1 homozygotes. There are 173 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 12 hem., cov: 23)

Exomes 𝑓: 0.00037 ( 1 hom. 161 hem. )

Consequence

SUV39H1
NM_003173.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.70

Variant links:

Genes affected

SUV39H1 (HGNC:11479): (SUV39H1 histone lysine methyltransferase) This gene encodes an evolutionarily-conserved protein containing an N-terminal chromodomain and a C-terminal SET domain. The encoded protein is a histone methyltransferase that trimethylates lysine 9 of histone H3, which results in transcriptional gene silencing. Loss of function of this gene disrupts heterochromatin formation and may cause chromosome instability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

SUV39H1 links:

ENSG00000232828 (HGNC:):

ENSG00000232828 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant X-48700705-C-T is Benign according to our data. Variant chrX-48700705-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660466.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-48700705-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.7 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUV39H1	NM_003173.4 link	c.780C>T	p.Thr260Thr	synonymous_variant	Exon 3 of 6	ENST00000376687.4	NP_003164.1	O43463-1
SUV39H1	NM_001282166.2 link	c.813C>T	p.Thr271Thr	synonymous_variant	Exon 3 of 6		NP_001269095.1	O43463-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SUV39H1	ENST00000376687.4 link	c.780C>T	p.Thr260Thr	synonymous_variant	Exon 3 of 6	1	NM_003173.4	ENSP00000365877.4	O43463-1
SUV39H1	ENST00000337852.10 link	c.813C>T	p.Thr271Thr	synonymous_variant	Exon 3 of 6	2		ENSP00000337976.6	O43463-2
ENSG00000232828	ENST00000416061.1 link	n.126G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.000240

AC:

AN:

112307

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

AN XY:

34477

show subpopulations

Gnomad AFR

AF:

0.0000647

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000933

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000736

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000414

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000401

AC:

AN:

182207

Hom.:

AF XY:

0.000524

AC XY:

AN XY:

66821

show subpopulations

Gnomad AFR exome

AF:

0.0000764

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00132

Gnomad FIN exome

AF:

0.0000635

Gnomad NFE exome

AF:

0.000542

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000374

AC:

410

AN:

1097645

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

161

AN XY:

363025

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000853

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.000379

Gnomad4 OTH exome

AF:

0.000261

GnomAD4 genome

AF:

0.000240

AC:

AN:

112307

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

AN XY:

34477

show subpopulations

Gnomad4 AFR

AF:

0.0000647

Gnomad4 AMR

AF:

0.0000933

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000736

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000414

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000253

EpiCase

AF:

0.000491

EpiControl

AF:

0.000654

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SUV39H1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.093

DANN

Benign

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over