16-75555936-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001077418.3(TMEM231):c.177G>A(p.Pro59Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,268 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 (★). Synonymous variant affecting the same amino acid position (i.e. P59P) has been classified as Benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
TMEM231
NM_001077418.3 synonymous
NM_001077418.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0770
Publications
2 publications found
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]
TMEM231 Gene-Disease associations (from GenCC):
- ciliopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Joubert syndrome 20Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- Joubert syndrome with oculorenal defectInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Meckel syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- orofaciodigital syndrome IIIInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 16-75555936-C-T is Benign according to our data. Variant chr16-75555936-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1977120.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.077 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TMEM231 | NM_001077418.3 | c.177G>A | p.Pro59Pro | synonymous_variant | Exon 2 of 7 | ENST00000258173.11 | NP_001070886.1 | |
| TMEM231 | NM_001077416.2 | c.336G>A | p.Pro112Pro | synonymous_variant | Exon 1 of 6 | NP_001070884.2 | ||
| TMEM231 | NR_074083.2 | n.220G>A | non_coding_transcript_exon_variant | Exon 2 of 7 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TMEM231 | ENST00000258173.11 | c.177G>A | p.Pro59Pro | synonymous_variant | Exon 2 of 7 | 1 | NM_001077418.3 | ENSP00000258173.5 | ||
| TMEM231 | ENST00000568377.5 | c.264G>A | p.Pro88Pro | synonymous_variant | Exon 1 of 6 | 1 | ENSP00000476267.1 | |||
| TMEM231 | ENST00000565067.5 | c.177G>A | p.Pro59Pro | synonymous_variant | Exon 2 of 6 | 5 | ENSP00000457254.1 | |||
| TMEM231 | ENST00000562410.5 | n.177G>A | non_coding_transcript_exon_variant | Exon 2 of 7 | 1 | ENSP00000454582.1 | ||||
| TMEM231 | ENST00000570006.5 | n.177G>A | non_coding_transcript_exon_variant | Exon 2 of 7 | 5 | ENSP00000455520.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000433 AC: 1AN: 231062 AF XY: 0.00000792 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
231062
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.89e-7 AC: 1AN: 1452268Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 721638 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1452268
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
721638
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33154
American (AMR)
AF:
AC:
0
AN:
43560
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25800
East Asian (EAS)
AF:
AC:
1
AN:
39326
South Asian (SAS)
AF:
AC:
0
AN:
84370
European-Finnish (FIN)
AF:
AC:
0
AN:
52198
Middle Eastern (MID)
AF:
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1108074
Other (OTH)
AF:
AC:
0
AN:
60034
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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<30
30-35
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Joubert syndrome 20;C3809352:Meckel syndrome, type 11 Benign:1
Jul 23, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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