rs372775075
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_001077418.3(TMEM231):c.223C>T(p.Pro75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,596,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P75P) has been classified as Likely benign.
Frequency
Consequence
NM_001077418.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM231 | NM_001077418.3 | c.223C>T | p.Pro75Ser | missense_variant | 2/7 | ENST00000258173.11 | |
TMEM231 | NM_001077416.2 | c.382C>T | p.Pro128Ser | missense_variant | 1/6 | ||
TMEM231 | NR_074083.2 | n.266C>T | non_coding_transcript_exon_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM231 | ENST00000258173.11 | c.223C>T | p.Pro75Ser | missense_variant | 2/7 | 1 | NM_001077418.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000183 AC: 4AN: 218742Hom.: 0 AF XY: 0.00000838 AC XY: 1AN XY: 119388
GnomAD4 exome AF: 0.0000692 AC: 100AN: 1444304Hom.: 0 Cov.: 30 AF XY: 0.0000698 AC XY: 50AN XY: 716582
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Joubert syndrome 20;C3809352:Meckel syndrome, type 11 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 128 of the TMEM231 protein (p.Pro128Ser). This variant is present in population databases (rs372775075, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with TMEM231-related conditions. ClinVar contains an entry for this variant (Variation ID: 445642). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 17, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 08, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at