chr13-49482767-A-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001160308.3(SETDB2):c.1187A>T(p.Lys396Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 1,611,890 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.028 ( 207 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 190 hom. )
Consequence
SETDB2
NM_001160308.3 missense
NM_001160308.3 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 1.58
Genes affected
SETDB2 (HGNC:20263): (SET domain bifurcated histone lysine methyltransferase 2) This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0018853843).
BP6
?
Variant 13-49482767-A-T is Benign according to our data. Variant chr13-49482767-A-T is described in ClinVar as [Benign]. Clinvar id is 786240.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETDB2 | NM_001160308.3 | c.1187A>T | p.Lys396Ile | missense_variant | 9/14 | ENST00000611815.2 | |
SETDB2-PHF11 | NR_135324.2 | n.2278A>T | non_coding_transcript_exon_variant | 10/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETDB2 | ENST00000611815.2 | c.1187A>T | p.Lys396Ile | missense_variant | 9/14 | 5 | NM_001160308.3 | P1 | |
SETDB2 | ENST00000354234.8 | c.1223A>T | p.Lys408Ile | missense_variant | 10/15 | 1 | |||
SETDB2 | ENST00000317257.12 | c.1187A>T | p.Lys396Ile | missense_variant | 8/13 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0278 AC: 4236AN: 152160Hom.: 206 Cov.: 33
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GnomAD3 exomes AF: 0.00741 AC: 1859AN: 250714Hom.: 106 AF XY: 0.00555 AC XY: 753AN XY: 135598
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GnomAD4 exome AF: 0.00270 AC: 3947AN: 1459612Hom.: 190 Cov.: 29 AF XY: 0.00228 AC XY: 1659AN XY: 726204
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GnomAD4 genome ? AF: 0.0279 AC: 4253AN: 152278Hom.: 207 Cov.: 33 AF XY: 0.0270 AC XY: 2010AN XY: 74466
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ESP6500AA
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439
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1139
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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 submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
REVEL
Uncertain
Sift4G
Benign
T;D;T;T
Polyphen
D;.;D;.
Vest4
MVP
MPC
1.1
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at