Genetic Variant TUBGCP5:p.Gly870Arg (chr15-23005536-C-T) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

TUBGCP5 links:

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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
TUBGCP5	NM_052903.6 link	c.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	UniProt
TUBGCP5	ENST00000615383.5 link	c.2608G>A	p.Gly870Arg	missense_variant	Exon 19 of 23	1	NM_052903.6	ENSP00000480316.1	Q96RT8-1
TUBGCP5	ENST00000620435.4 link	c.2608G>A	p.Gly870Arg	missense_variant	Exon 19 of 22	2		ENSP00000481853.1	Q96RT8-2
TUBGCP5	ENST00000610294.1 link	c.571G>A	p.Gly191Arg	missense_variant	Exon 5 of 5	5		ENSP00000483015.1	A0A087X006
TUBGCP5	ENST00000614508.4 link	n.2608G>A		non_coding_transcript_exon_variant	Exon 19 of 24	5		ENSP00000484566.1	A0A087X1Z1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152122

Hom.:

Cov.:

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:

AN:

251426

Hom.:

AF XY:

0.0000515

AC XY:

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:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

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:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

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.:

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over