rs148601529
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_020461.4(TUBGCP6):c.3898C>T(p.His1300Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00008 in 1,612,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. H1300H) has been classified as Likely benign.
Frequency
Consequence
NM_020461.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBGCP6 | NM_020461.4 | c.3898C>T | p.His1300Tyr | missense_variant | 16/25 | ENST00000248846.10 | |
TUBGCP6 | XR_001755343.3 | n.4462C>T | non_coding_transcript_exon_variant | 16/20 | |||
TUBGCP6 | XR_938347.3 | n.4462C>T | non_coding_transcript_exon_variant | 16/23 | |||
TUBGCP6 | XR_007067982.1 | n.3049-446C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBGCP6 | ENST00000248846.10 | c.3898C>T | p.His1300Tyr | missense_variant | 16/25 | 1 | NM_020461.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000447 AC: 68AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000105 AC: 26AN: 247100Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 134328
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1460542Hom.: 0 Cov.: 39 AF XY: 0.0000330 AC XY: 24AN XY: 726576
GnomAD4 genome ? AF: 0.000466 AC: 71AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33AN XY: 74502
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 13, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1300 of the TUBGCP6 protein (p.His1300Tyr). This variant is present in population databases (rs148601529, gnomAD 0.2%). 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: 437146). 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | 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