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GeneBe

X-48700705-C-T

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.Thr260=) 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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.7 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SUV39H1NM_003173.4 linkuse as main transcriptc.780C>T p.Thr260= synonymous_variant 3/6 ENST00000376687.4
SUV39H1NM_001282166.2 linkuse as main transcriptc.813C>T p.Thr271= synonymous_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SUV39H1ENST00000376687.4 linkuse as main transcriptc.780C>T p.Thr260= synonymous_variant 3/61 NM_003173.4 P1O43463-1
ENST00000416061.1 linkuse as main transcriptn.126G>A splice_region_variant, non_coding_transcript_exon_variant 2/33
SUV39H1ENST00000337852.10 linkuse as main transcriptc.813C>T p.Thr271= synonymous_variant 3/62 O43463-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000240
AC:
27
AN:
112307
Hom.:
0
Cov.:
23
AF XY:
0.000348
AC XY:
12
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:
73
AN:
182207
Hom.:
0
AF XY:
0.000524
AC XY:
35
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.:
1
Cov.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000240
AC:
27
AN:
112307
Hom.:
0
Cov.:
23
AF XY:
0.000348
AC XY:
12
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.:
2
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
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2022SUV39H1: 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.

Other links and lift over

dbSNP: rs143860178; hg19: chrX-48559096; API