Variant X-48700687-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003173.4(SUV39H1):c.762T>C(p.Arg254Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,210,614 control chromosomes in the GnomAD database, including 9 homozygotes. There are 340 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., 148 hem., cov: 23)

Exomes 𝑓: 0.00059 ( 3 hom. 192 hem. )

Consequence

SUV39H1
NM_003173.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -8.95

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-48700687-T-C is Benign according to our data. Variant chrX-48700687-T-C is described in ClinVar as [Benign]. Clinvar id is 730023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.95 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (570/112510) while in subpopulation AFR AF= 0.017 (528/31034). AF 95% confidence interval is 0.0158. There are 6 homozygotes in gnomad4. There are 148 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUV39H1	NM_003173.4 linkuse as main transcript	c.762T>C	p.Arg254Arg	synonymous_variant	3/6	ENST00000376687.4	NP_003164.1	O43463-1
SUV39H1	NM_001282166.2 linkuse as main transcript	c.795T>C	p.Arg265Arg	synonymous_variant	3/6		NP_001269095.1	O43463-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SUV39H1	ENST00000376687.4 linkuse as main transcript	c.762T>C	p.Arg254Arg	synonymous_variant	3/6	1	NM_003173.4	ENSP00000365877.4	O43463-1
SUV39H1	ENST00000337852.10 linkuse as main transcript	c.795T>C	p.Arg265Arg	synonymous_variant	3/6	2		ENSP00000337976.6	O43463-2
ENSG00000232828	ENST00000416061.1 linkuse as main transcript	n.144A>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

570

AN:

112459

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

148

AN XY:

34617

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.000752

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.0000940

Gnomad OTH

AF:

0.00528

GnomAD3 exomes

AF:

0.00164

AC:

299

AN:

182836

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

67336

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.000669

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000858

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.000595

AC:

653

AN:

1098104

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

192

AN XY:

363460

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.000774

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000321

Gnomad4 OTH exome

AF:

0.00135

GnomAD4 genome

AF:

0.00507

AC:

570

AN:

112510

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

148

AN XY:

34678

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.000752

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000940

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.00592

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.13

DANN

Benign

0.69

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