chr3-47120625-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014159.7(SETD2):c.4011A>G(p.Glu1337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,614,146 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00072 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000065 ( 1 hom. )
Consequence
SETD2
NM_014159.7 synonymous
NM_014159.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.156
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=-0.71).
BP6
?
Variant 3-47120625-T-C is Benign according to our data. Variant chr3-47120625-T-C is described in ClinVar as [Benign]. Clinvar id is 542235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.156 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000722 (110/152348) while in subpopulation AFR AF= 0.00257 (107/41588). AF 95% confidence interval is 0.00218. There are 1 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 110 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD2 | NM_014159.7 | c.4011A>G | p.Glu1337= | synonymous_variant | 3/21 | ENST00000409792.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD2 | ENST00000409792.4 | c.4011A>G | p.Glu1337= | synonymous_variant | 3/21 | 5 | NM_014159.7 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000723 AC: 110AN: 152230Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000207 AC: 52AN: 251276Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135810
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GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461798Hom.: 1 Cov.: 33 AF XY: 0.0000509 AC XY: 37AN XY: 727194
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GnomAD4 genome ? AF: 0.000722 AC: 110AN: 152348Hom.: 1 Cov.: 32 AF XY: 0.000765 AC XY: 57AN XY: 74500
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Luscan-Lumish syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 02, 2021 | - - |
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