rs587777969
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_014159.7(SETD2):c.4839+332G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000978 in 450,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000097 ( 0 hom. )
Consequence
SETD2
NM_014159.7 intron
NM_014159.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.621
Genes affected
SETD2 (HGNC:18420): (SET domain containing 2, histone lysine methyltransferase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein belonging to a class of huntingtin interacting proteins characterized by WW motifs. This protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000988 (15/151852) while in subpopulation NFE AF= 0.000221 (15/67962). AF 95% confidence interval is 0.000135. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD2 | NM_014159.7 | c.4839+332G>T | intron_variant | ENST00000409792.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD2 | ENST00000409792.4 | c.4839+332G>T | intron_variant | 5 | NM_014159.7 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000988 AC: 15AN: 151852Hom.: 0 Cov.: 29
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GnomAD3 exomes AF: 0.0000506 AC: 6AN: 118652Hom.: 0 AF XY: 0.0000460 AC XY: 3AN XY: 65256
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GnomAD4 exome AF: 0.0000972 AC: 29AN: 298204Hom.: 0 Cov.: 0 AF XY: 0.0000823 AC XY: 14AN XY: 170170
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GnomAD4 genome ? AF: 0.0000988 AC: 15AN: 151852Hom.: 0 Cov.: 29 AF XY: 0.0000674 AC XY: 5AN XY: 74176
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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