rs34758634
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000391.4(TPP1):c.553C>T(p.Arg185Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000548 in 1,614,148 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R185G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000391.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPP1 | NM_000391.4 | c.553C>T | p.Arg185Cys | missense_variant | 6/13 | ENST00000299427.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPP1 | ENST00000299427.12 | c.553C>T | p.Arg185Cys | missense_variant | 6/13 | 1 | NM_000391.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00302 AC: 460AN: 152164Hom.: 4 Cov.: 31
GnomAD3 exomes AF: 0.000867 AC: 218AN: 251352Hom.: 2 AF XY: 0.000611 AC XY: 83AN XY: 135864
GnomAD4 exome AF: 0.000290 AC: 424AN: 1461866Hom.: 1 Cov.: 42 AF XY: 0.000215 AC XY: 156AN XY: 727238
GnomAD4 genome AF: 0.00303 AC: 461AN: 152282Hom.: 4 Cov.: 31 AF XY: 0.00278 AC XY: 207AN XY: 74462
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 19, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 05, 2024 | 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. - |
Neuronal ceroid lipofuscinosis 2 Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 18, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at