rs767711440
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001044385.3(TMEM237):c.297A>G(p.Gln99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000319 in 1,566,080 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
TMEM237
NM_001044385.3 synonymous
NM_001044385.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.544
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 2-201633409-T-C is Benign according to our data. Variant chr2-201633409-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.544 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM237 | NM_001044385.3 | c.297A>G | p.Gln99= | synonymous_variant | 6/13 | ENST00000409883.7 | |
TMEM237 | NM_152388.4 | c.273A>G | p.Gln91= | synonymous_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM237 | ENST00000409883.7 | c.297A>G | p.Gln99= | synonymous_variant | 6/13 | 5 | NM_001044385.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000555 AC: 1AN: 180252Hom.: 0 AF XY: 0.0000104 AC XY: 1AN XY: 95858
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GnomAD4 exome AF: 0.0000311 AC: 44AN: 1413890Hom.: 0 Cov.: 29 AF XY: 0.0000315 AC XY: 22AN XY: 699088
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74368
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Joubert syndrome 14 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at