dbSNP rs149154554: TUBGCP5:p.Thr974Ala (chr15-23003072-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_052903.6(TUBGCP5):c.2920A>G(p.Thr974Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,614,108 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 36 hom. )

Consequence

TUBGCP5
NM_052903.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.78

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017676145).

BP6

Variant 15-23003072-T-C is Benign according to our data. Variant chr15-23003072-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 717098.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP5	NM_052903.6 link	c.2920A>G	p.Thr974Ala	missense_variant	Exon 21 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.2920A>G	p.Thr974Ala	missense_variant	Exon 21 of 23	1	NM_052903.6	ENSP00000480316.1	Q96RT8-1
TUBGCP5	ENST00000620435.4 link	c.2920A>G	p.Thr974Ala	missense_variant	Exon 21 of 22	2		ENSP00000481853.1	Q96RT8-2
TUBGCP5	ENST00000614508.4 link	n.2920A>G		non_coding_transcript_exon_variant	Exon 21 of 24	5		ENSP00000484566.1	A0A087X1Z1
TUBGCP5	ENST00000620238.1 link	n.*19A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00395

AC:

601

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00617

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00392

AC:

986

AN:

251342

Hom.:

AF XY:

0.00386

AC XY:

524

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.00574

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00380

AC:

5558

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

2776

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.00414

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00395

AC:

601

AN:

152280

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.00617

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.00241

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.78

DANN

Benign

0.69

DEOGEN2

Benign

0.015

T;.

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.018

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.098

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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