rs375822537
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_025009.5(CEP135):c.1920G>A(p.Ser640=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,594,292 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 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
CEP135
NM_025009.5 synonymous
NM_025009.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.885
Genes affected
CEP135 (HGNC:29086): (centrosomal protein 135) This gene encodes a centrosomal protein, which acts as a scaffolding protein during early centriole biogenesis, and is also required for centriole-centriole cohesion during interphase. Mutations in this gene are associated with autosomal recessive primary microcephaly-8. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 4-55991996-G-A is Benign according to our data. Variant chr4-55991996-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.885 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000111 (160/1442048) while in subpopulation MID AF= 0.00123 (7/5704). AF 95% confidence interval is 0.000575. There are 0 homozygotes in gnomad4_exome. There are 81 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP135 | NM_025009.5 | c.1920G>A | p.Ser640= | synonymous_variant | 15/26 | ENST00000257287.5 | |
CEP135 | XM_006714055.4 | c.1887G>A | p.Ser629= | synonymous_variant | 15/26 | ||
CEP135 | XM_005265788.5 | c.849G>A | p.Ser283= | synonymous_variant | 8/19 | ||
CEP135 | XM_011534412.2 | c.390G>A | p.Ser130= | synonymous_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP135 | ENST00000257287.5 | c.1920G>A | p.Ser640= | synonymous_variant | 15/26 | 1 | NM_025009.5 | P1 | |
CEP135 | ENST00000506202.1 | n.1870G>A | non_coding_transcript_exon_variant | 8/19 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152126Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000221 AC: 54AN: 244730Hom.: 0 AF XY: 0.000226 AC XY: 30AN XY: 132552
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GnomAD4 exome AF: 0.000111 AC: 160AN: 1442048Hom.: 0 Cov.: 28 AF XY: 0.000113 AC XY: 81AN XY: 718010
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74440
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | CEP135: BP4, BP7 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 05, 2016 | - - |
CEP135-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 23, 2021 | 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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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