rs142435821
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_020461.4(TUBGCP6):c.1193C>T(p.Ser398Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000733 in 1,610,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S398S) has been classified as Likely benign.
Frequency
Consequence
NM_020461.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBGCP6 | NM_020461.4 | c.1193C>T | p.Ser398Leu | missense_variant | 4/25 | ENST00000248846.10 | |
TUBGCP6 | XR_001755343.3 | n.1757C>T | non_coding_transcript_exon_variant | 4/20 | |||
TUBGCP6 | XR_007067982.1 | n.1757C>T | non_coding_transcript_exon_variant | 4/19 | |||
TUBGCP6 | XR_938347.3 | n.1757C>T | non_coding_transcript_exon_variant | 4/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBGCP6 | ENST00000248846.10 | c.1193C>T | p.Ser398Leu | missense_variant | 4/25 | 1 | NM_020461.4 | P1 | |
TUBGCP6 | ENST00000439308.6 | c.1193C>T | p.Ser398Leu | missense_variant | 4/25 | 1 | |||
TUBGCP6 | ENST00000498611.5 | n.1726C>T | non_coding_transcript_exon_variant | 4/23 | 1 | ||||
TUBGCP6 | ENST00000434349.1 | c.425C>T | p.Ser142Leu | missense_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000598 AC: 91AN: 152200Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000551 AC: 134AN: 243190Hom.: 0 AF XY: 0.000530 AC XY: 70AN XY: 132138
GnomAD4 exome AF: 0.000747 AC: 1090AN: 1458646Hom.: 0 Cov.: 31 AF XY: 0.000704 AC XY: 511AN XY: 725422
GnomAD4 genome ? AF: 0.000597 AC: 91AN: 152318Hom.: 1 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 398 of the TUBGCP6 protein (p.Ser398Leu). This variant is present in population databases (rs142435821, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TUBGCP6-related conditions. ClinVar contains an entry for this variant (Variation ID: 437160). 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. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | TUBGCP6: BP4 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 23, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2022 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at