16-75545349-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001077418.3(TMEM231):c.582+3A>G 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 0.00308 in 1,612,598 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.017 ( 60 hom., cov: 22)
Exomes 𝑓: 0.0017 ( 63 hom. )
Consequence
TMEM231
NM_001077418.3 splice_donor_region, intron
NM_001077418.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.1897
2
Clinical Significance
Conservation
PhyloP100: 2.22
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 16-75545349-T-C is Benign according to our data. Variant chr16-75545349-T-C is described in ClinVar as [Benign]. Clinvar id is 130589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75545349-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM231 | NM_001077418.3 | c.582+3A>G | splice_donor_region_variant, intron_variant | ENST00000258173.11 | |||
TMEM231 | NM_001077416.2 | c.741+3A>G | splice_donor_region_variant, intron_variant | ||||
TMEM231 | NR_074083.2 | n.748+3A>G | splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM231 | ENST00000258173.11 | c.582+3A>G | splice_donor_region_variant, intron_variant | 1 | NM_001077418.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0166 AC: 2521AN: 152108Hom.: 58 Cov.: 22
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GnomAD3 exomes AF: 0.00415 AC: 1031AN: 248492Hom.: 25 AF XY: 0.00299 AC XY: 403AN XY: 134784
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GnomAD4 exome AF: 0.00166 AC: 2417AN: 1460372Hom.: 63 Cov.: 31 AF XY: 0.00138 AC XY: 1003AN XY: 726248
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GnomAD4 genome AF: 0.0167 AC: 2544AN: 152226Hom.: 60 Cov.: 22 AF XY: 0.0162 AC XY: 1205AN XY: 74418
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 25, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Joubert syndrome 20;C3809352:Meckel syndrome, type 11 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at