rs74411816
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_001044385.3(TMEM237):c.396-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,612,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
TMEM237
NM_001044385.3 splice_polypyrimidine_tract, intron
NM_001044385.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.66
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 2-201632222-G-A is Benign according to our data. Variant chr2-201632222-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257319.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 = 0.0019 (290/152244) while in subpopulation AFR AF= 0.00645 (268/41552). AF 95% confidence interval is 0.00581. There are 1 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM237 | NM_001044385.3 | c.396-14C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000409883.7 | |||
TMEM237 | NM_152388.4 | c.372-14C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM237 | ENST00000409883.7 | c.396-14C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001044385.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00189 AC: 288AN: 152126Hom.: 1 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
288
AN:
152126
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000479 AC: 119AN: 248308Hom.: 0 AF XY: 0.000408 AC XY: 55AN XY: 134678
GnomAD3 exomes
AF:
AC:
119
AN:
248308
Hom.:
AF XY:
AC XY:
55
AN XY:
134678
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000183 AC: 267AN: 1459784Hom.: 0 Cov.: 30 AF XY: 0.000164 AC XY: 119AN XY: 725932
GnomAD4 exome
AF:
AC:
267
AN:
1459784
Hom.:
Cov.:
30
AF XY:
AC XY:
119
AN XY:
725932
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00190 AC: 290AN: 152244Hom.: 1 Cov.: 32 AF XY: 0.00173 AC XY: 129AN XY: 74436
GnomAD4 genome
?
AF:
AC:
290
AN:
152244
Hom.:
Cov.:
32
AF XY:
AC XY:
129
AN XY:
74436
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
3
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
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 | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2021 | - - |
Joubert syndrome 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at