rs201636741
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2
The NM_001077418.3(TMEM231):c.498G>A(p.Pro166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00082 in 1,605,626 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0043 ( 5 hom., cov: 21)
Exomes 𝑓: 0.00047 ( 3 hom. )
Consequence
TMEM231
NM_001077418.3 synonymous
NM_001077418.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.67
Genes affected
TMEM231 (HGNC:37234): (transmembrane protein 231) This gene encodes a transmembrane protein, which is a component of the B9 complex involved in the formation of the diffusion barrier between the cilia and plasma membrane. Mutations in this gene cause Joubert syndrome (JBTS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 16-75545436-C-T is Benign according to our data. Variant chr16-75545436-C-T is described in ClinVar as [Benign]. Clinvar id is 385987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00428 (638/149212) while in subpopulation AFR AF= 0.0144 (583/40402). AF 95% confidence interval is 0.0135. There are 5 homozygotes in gnomad4. There are 315 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM231 | NM_001077418.3 | c.498G>A | p.Pro166= | synonymous_variant | 4/7 | ENST00000258173.11 | |
TMEM231 | NM_001077416.2 | c.657G>A | p.Pro219= | synonymous_variant | 3/6 | ||
TMEM231 | NR_074083.2 | n.664G>A | non_coding_transcript_exon_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM231 | ENST00000258173.11 | c.498G>A | p.Pro166= | synonymous_variant | 4/7 | 1 | NM_001077418.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00429 AC: 639AN: 149096Hom.: 5 Cov.: 21
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GnomAD3 exomes AF: 0.00121 AC: 300AN: 246996Hom.: 0 AF XY: 0.000999 AC XY: 134AN XY: 134068
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GnomAD4 exome AF: 0.000466 AC: 678AN: 1456414Hom.: 3 Cov.: 28 AF XY: 0.000407 AC XY: 295AN XY: 724352
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GnomAD4 genome ? AF: 0.00428 AC: 638AN: 149212Hom.: 5 Cov.: 21 AF XY: 0.00434 AC XY: 315AN XY: 72662
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 21, 2022 | - - |
Joubert syndrome 20;C3809352:Meckel syndrome, type 11 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 27, 2018 | - - |
Computational scores
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Name
Calibrated prediction
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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
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at