chr3-9453872-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001080517.3(SETD5):c.2476+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000842 in 1,561,362 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 0.00043 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00089 ( 1 hom. )
Consequence
SETD5
NM_001080517.3 splice_donor_region, intron
NM_001080517.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001365
2
Clinical Significance
Conservation
PhyloP100: -3.13
Genes affected
SETD5 (HGNC:25566): (SET domain containing 5) This function of this gene has yet to be determined but based on sequence similarity to other SET domain proteins it may function as a histone methyltransferase. Mutations in this gene have been associated with an autosomal dominant form of intellectual disability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 3-9453872-C-T is Benign according to our data. Variant chr3-9453872-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000433 (66/152258) while in subpopulation NFE AF= 0.000779 (53/68014). AF 95% confidence interval is 0.000612. There are 0 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 66 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD5 | NM_001080517.3 | c.2476+4C>T | splice_donor_region_variant, intron_variant | ENST00000402198.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD5 | ENST00000402198.7 | c.2476+4C>T | splice_donor_region_variant, intron_variant | 5 | NM_001080517.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000434 AC: 66AN: 152140Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000520 AC: 105AN: 201878Hom.: 1 AF XY: 0.000570 AC XY: 63AN XY: 110590
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GnomAD4 exome AF: 0.000886 AC: 1248AN: 1409104Hom.: 1 Cov.: 31 AF XY: 0.000835 AC XY: 585AN XY: 700214
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GnomAD4 genome AF: 0.000433 AC: 66AN: 152258Hom.: 0 Cov.: 31 AF XY: 0.000416 AC XY: 31AN XY: 74454
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 14, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | SETD5: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 24, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
SETD5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 26, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at