chr3-9433896-C-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001080517.3(SETD5):c.123C>A(p.Ser41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,828 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
SETD5
NM_001080517.3 synonymous
NM_001080517.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.27
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 3-9433896-C-A is Benign according to our data. Variant chr3-9433896-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 713197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.27 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000526 (8/152194) while in subpopulation EAS AF= 0.00116 (6/5168). AF 95% confidence interval is 0.000505. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD5 | NM_001080517.3 | c.123C>A | p.Ser41= | synonymous_variant | 4/23 | ENST00000402198.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD5 | ENST00000402198.7 | c.123C>A | p.Ser41= | synonymous_variant | 4/23 | 5 | NM_001080517.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152076Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000116 AC: 29AN: 249132Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135138
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461634Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727100
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 03, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | SETD5: BP4, BS1 - |
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