chr1-150963063-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001366418.1(SETDB1):c.3384G>A(p.Ala1128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,050 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000072 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
SETDB1
NM_001366418.1 synonymous
NM_001366418.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.67
Genes affected
SETDB1 (HGNC:10761): (SET domain bifurcated histone lysine methyltransferase 1) This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription dysfunction likely play a role in the disease pathogenesis. Alternatively spliced transcript variants of this gene have been described.[provided by RefSeq, Jun 2011]
CERS2 (HGNC:14076): (ceramide synthase 2) This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
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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=-0.65).
BP6
Variant 1-150963063-G-A is Benign according to our data. Variant chr1-150963063-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639165.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.67 with no splicing effect.
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETDB1 | NM_001366418.1 | c.3384G>A | p.Ala1128= | synonymous_variant | 19/22 | ENST00000692827.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETDB1 | ENST00000692827.1 | c.3384G>A | p.Ala1128= | synonymous_variant | 19/22 | NM_001366418.1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152174Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251460Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135908
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 727240
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152174Hom.: 1 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74336
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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 submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | SETDB1: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at