rs1553437721
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_017849.4(TMEM127):c.210C>T(p.Asp70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TMEM127
NM_017849.4 synonymous
NM_017849.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.787
Genes affected
TMEM127 (HGNC:26038): (transmembrane protein 127) This gene encodes a transmembrane protein with four predicted transmembrane domains. The protein is associated with a subpopulation of vesicular organelles corresponding to early endosomal structures, with the Golgi, and with lysosomes, and may participate in protein trafficking between these structures. Mutations in this gene and several other genes cause pheochromocytomas. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 2-96265172-G-A is Benign according to our data. Variant chr2-96265172-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 463840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.787 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM127 | NM_017849.4 | c.210C>T | p.Asp70= | synonymous_variant | 2/4 | ENST00000258439.8 | |
TMEM127 | NM_001193304.3 | c.210C>T | p.Asp70= | synonymous_variant | 2/4 | ||
TMEM127 | NM_001407283.1 | c.-9+697C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM127 | ENST00000258439.8 | c.210C>T | p.Asp70= | synonymous_variant | 2/4 | 1 | NM_017849.4 | P1 | |
TMEM127 | ENST00000432959.1 | c.210C>T | p.Asp70= | synonymous_variant | 2/4 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1458890Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 725582
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1458890
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
725582
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 22, 2019 | 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. - |
Hereditary pheochromocytoma-paraganglioma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2022 | - - |
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