rs763476625
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_017849.4(TMEM127):c.88A>G(p.Ser30Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00032 in 1,552,786 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S30I) has been classified as Uncertain significance.
Frequency
Consequence
NM_017849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM127 | NM_017849.4 | c.88A>G | p.Ser30Gly | missense_variant | 2/4 | ENST00000258439.8 | |
TMEM127 | NM_001193304.3 | c.88A>G | p.Ser30Gly | missense_variant | 2/4 | ||
TMEM127 | NM_001407283.1 | c.-9+575A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM127 | ENST00000258439.8 | c.88A>G | p.Ser30Gly | missense_variant | 2/4 | 1 | NM_017849.4 | P1 | |
TMEM127 | ENST00000432959.1 | c.88A>G | p.Ser30Gly | missense_variant | 2/4 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000599 AC: 9AN: 150266Hom.: 0 AF XY: 0.0000726 AC XY: 6AN XY: 82604
GnomAD4 exome AF: 0.000344 AC: 482AN: 1400576Hom.: 0 Cov.: 31 AF XY: 0.000318 AC XY: 220AN XY: 692898
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74374
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 16, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 09, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Pheochromocytoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 06, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary pheochromocytoma-paraganglioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 30 of the TMEM127 protein (p.Ser30Gly). This variant is present in population databases (rs763476625, gnomAD 0.02%). 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: 405201). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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