rs1231130879
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017849.4(TMEM127):āc.71C>Gā(p.Pro24Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,538,266 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. P24P) has been classified as Likely benign.
Frequency
Consequence
NM_017849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM127 | NM_017849.4 | c.71C>G | p.Pro24Arg | missense_variant | 2/4 | ENST00000258439.8 | |
TMEM127 | NM_001193304.3 | c.71C>G | p.Pro24Arg | missense_variant | 2/4 | ||
TMEM127 | NM_001407283.1 | c.-9+558C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM127 | ENST00000258439.8 | c.71C>G | p.Pro24Arg | missense_variant | 2/4 | 1 | NM_017849.4 | P1 | |
TMEM127 | ENST00000432959.1 | c.71C>G | p.Pro24Arg | missense_variant | 2/4 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32
GnomAD4 exome AF: 7.21e-7 AC: 1AN: 1386048Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1AN XY: 684108
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 27, 2023 | The p.P24R variant (also known as c.71C>G), located in coding exon 1 of the TMEM127 gene, results from a C to G substitution at nucleotide position 71. The proline at codon 24 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hereditary pheochromocytoma-paraganglioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 24 of the TMEM127 protein (p.Pro24Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with TMEM127-related conditions. ClinVar contains an entry for this variant (Variation ID: 532522). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at