chr22-50217780-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020461.4(TUBGCP6):ā€‹c.5416T>Cā€‹(p.Phe1806Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Synonymous variant affecting the same amino acid position (i.e. F1806F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

6
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.15
Variant links:
Genes affected
TUBGCP6 (HGNC:18127): (tubulin gamma complex component 6) The protein encoded by this gene is part of a large multisubunit complex required for microtubule nucleation at the centrosome. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TUBGCP6NM_020461.4 linkuse as main transcriptc.5416T>C p.Phe1806Leu missense_variant 25/25 ENST00000248846.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TUBGCP6ENST00000248846.10 linkuse as main transcriptc.5416T>C p.Phe1806Leu missense_variant 25/251 NM_020461.4 P1Q96RT7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461772
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMay 13, 2021This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 1806 of the TUBGCP6 protein (p.Phe1806Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant has not been reported in the literature in individuals with TUBGCP6-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Benign
-0.040
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.28
T;.
Eigen
Benign
-0.042
Eigen_PC
Benign
-0.039
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.86
D;T
M_CAP
Benign
0.068
D
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-5.0
D;D
REVEL
Uncertain
0.29
Sift
Pathogenic
0.0
D;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.99
D;.
Vest4
0.56
MutPred
0.63
Loss of helix (P = 0.1706);.;
MVP
0.32
MPC
0.36
ClinPred
0.99
D
GERP RS
3.9
Varity_R
0.86
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50656209; API