15-23005536-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052903.6(TUBGCP5):​c.2608G>A​(p.Gly870Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TUBGCP5
NM_052903.6 missense

Scores

1
2
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96
Variant links:
Genes affected
TUBGCP5 (HGNC:18600): (tubulin gamma complex component 5) Enables microtubule binding activity. Involved in microtubule nucleation. Located in centrosome and cytosol. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21985894).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUBGCP5NM_052903.6 linkc.2608G>A p.Gly870Arg missense_variant Exon 19 of 23 ENST00000615383.5 NP_443135.3 Q96RT8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUBGCP5ENST00000615383.5 linkc.2608G>A p.Gly870Arg missense_variant Exon 19 of 23 1 NM_052903.6 ENSP00000480316.1 Q96RT8-1
TUBGCP5ENST00000620435.4 linkc.2608G>A p.Gly870Arg missense_variant Exon 19 of 22 2 ENSP00000481853.1 Q96RT8-2
TUBGCP5ENST00000610294.1 linkc.571G>A p.Gly191Arg missense_variant Exon 5 of 5 5 ENSP00000483015.1 A0A087X006
TUBGCP5ENST00000614508.4 linkn.2608G>A non_coding_transcript_exon_variant Exon 19 of 24 5 ENSP00000484566.1 A0A087X1Z1

Frequencies

GnomAD3 genomes
AF:
0.000289
AC:
44
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000756
AC:
19
AN:
251426
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.0000179
AC XY:
13
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000866
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.000289
AC:
44
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.00106
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000922
Hom.:
0
Bravo
AF:
0.000283

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2608G>A (p.G870R) alteration is located in exon 19 (coding exon 19) of the TUBGCP5 gene. This alteration results from a G to A substitution at nucleotide position 2608, causing the glycine (G) at amino acid position 870 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_noAF
Pathogenic
0.44
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.020
T;.
LIST_S2
Benign
0.76
T;T
MetaRNN
Benign
0.22
T;T
Sift4G
Uncertain
0.019
D;D
Vest4
0.42
gMVP
0.64

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142514694; hg19: chr15-22867532; API