chr16-75540054-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001077418.3(TMEM231):c.891G>A(p.Val297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 1,613,694 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0059 ( 74 hom. )
Consequence
TMEM231
NM_001077418.3 synonymous
NM_001077418.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.364
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 16-75540054-C-T is Benign according to our data. Variant chr16-75540054-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212404.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.364 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00454 (692/152328) while in subpopulation SAS AF= 0.0261 (126/4834). AF 95% confidence interval is 0.0224. There are 3 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM231 | NM_001077418.3 | c.891G>A | p.Val297= | synonymous_variant | 7/7 | ENST00000258173.11 | |
TMEM231 | NM_001077416.2 | c.1050G>A | p.Val350= | synonymous_variant | 6/6 | ||
TMEM231 | NR_074083.2 | n.1057G>A | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM231 | ENST00000258173.11 | c.891G>A | p.Val297= | synonymous_variant | 7/7 | 1 | NM_001077418.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00453 AC: 690AN: 152210Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00753 AC: 1873AN: 248802Hom.: 24 AF XY: 0.00907 AC XY: 1224AN XY: 135000
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GnomAD4 exome AF: 0.00585 AC: 8555AN: 1461366Hom.: 74 Cov.: 31 AF XY: 0.00670 AC XY: 4872AN XY: 726954
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GnomAD4 genome AF: 0.00454 AC: 692AN: 152328Hom.: 3 Cov.: 32 AF XY: 0.00505 AC XY: 376AN XY: 74480
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 10, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 21, 2017 | 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 31, 2024 | - - |
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