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GeneBe

X-48700687-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003173.4(SUV39H1):c.762T>C(p.Arg254=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.89).
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-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_single_submitter, 1 stars.
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=-8.95 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    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 Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SUV39H1NM_003173.4 linkuse as main transcriptc.762T>C p.Arg254= synonymous_variant 3/6 ENST00000376687.4
SUV39H1NM_001282166.2 linkuse as main transcriptc.795T>C p.Arg265= synonymous_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SUV39H1ENST00000376687.4 linkuse as main transcriptc.762T>C p.Arg254= synonymous_variant 3/61 NM_003173.4 P1O43463-1
ENST00000416061.1 linkuse as main transcriptn.144A>G non_coding_transcript_exon_variant 2/33
SUV39H1ENST00000337852.10 linkuse as main transcriptc.795T>C p.Arg265= synonymous_variant 3/62 O43463-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00507
AC:
570
AN:
112459
Hom.:
6
Cov.:
23
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.:
3
AF XY:
0.00114
AC XY:
77
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.:
3
Cov.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00507
AC:
570
AN:
112510
Hom.:
6
Cov.:
23
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.:
12
Bravo
AF:
0.00592
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 26, 2018- -

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.

Other links and lift over

dbSNP: rs141290793; hg19: chrX-48559078; API