rs77570029
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001044385.3(TMEM237):āc.1134T>Cā(p.Tyr378=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,596,412 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0019 ( 1 hom., cov: 31)
Exomes š: 0.00020 ( 3 hom. )
Consequence
TMEM237
NM_001044385.3 synonymous
NM_001044385.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.313
Genes affected
TMEM237 (HGNC:14432): (transmembrane protein 237) The protein encoded by this gene is a tetraspanin protein that is thought to be involved in WNT signaling. Defects in this gene are a cause of Joubert syndrome-14. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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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=-0.81).
BP6
?
Variant 2-201626051-A-G is Benign according to our data. Variant chr2-201626051-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257315.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 = 0.00193 (294/152226) while in subpopulation AFR AF= 0.00655 (272/41522). AF 95% confidence interval is 0.00591. There are 1 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM237 | NM_001044385.3 | c.1134T>C | p.Tyr378= | synonymous_variant | 12/13 | ENST00000409883.7 | |
TMEM237 | NM_152388.4 | c.1110T>C | p.Tyr370= | synonymous_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM237 | ENST00000409883.7 | c.1134T>C | p.Tyr378= | synonymous_variant | 12/13 | 5 | NM_001044385.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00190 AC: 289AN: 152108Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000468 AC: 104AN: 222278Hom.: 0 AF XY: 0.000376 AC XY: 45AN XY: 119758
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GnomAD4 exome AF: 0.000197 AC: 284AN: 1444186Hom.: 3 Cov.: 30 AF XY: 0.000184 AC XY: 132AN XY: 716568
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GnomAD4 genome ? AF: 0.00193 AC: 294AN: 152226Hom.: 1 Cov.: 31 AF XY: 0.00180 AC XY: 134AN XY: 74424
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 02, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 30, 2018 | - - |
Joubert syndrome 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 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