rs113560046
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014159.7(SETD2):c.4059C>T(p.Ser1353=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,614,020 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 Benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
SETD2
NM_014159.7 synonymous
NM_014159.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0810
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 3-47120577-G-A is Benign according to our data. Variant chr3-47120577-G-A is described in ClinVar as [Benign]. Clinvar id is 475516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.081 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00101 (153/152206) while in subpopulation AFR AF= 0.00344 (143/41528). AF 95% confidence interval is 0.00298. There are 0 homozygotes in gnomad4. There are 73 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 153 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD2 | NM_014159.7 | c.4059C>T | p.Ser1353= | synonymous_variant | 3/21 | ENST00000409792.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD2 | ENST00000409792.4 | c.4059C>T | p.Ser1353= | synonymous_variant | 3/21 | 5 | NM_014159.7 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000999 AC: 152AN: 152088Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000279 AC: 70AN: 251048Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135768
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GnomAD4 exome AF: 0.000119 AC: 174AN: 1461814Hom.: 0 Cov.: 33 AF XY: 0.000111 AC XY: 81AN XY: 727216
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GnomAD4 genome ? AF: 0.00101 AC: 153AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.000981 AC XY: 73AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Luscan-Lumish syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | SETD2: BS1, BS2 - |
Computational scores
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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