rs34273213

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020461.4(TUBGCP6):c.1118C>T(p.Pro373Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00064 in 1,585,532 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 4 hom. )

Consequence

TUBGCP6
NM_020461.4 missense, splice_region

Scores

Splicing: ADA: 0.00001693

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.198

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]

TUBGCP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046064854).

BP6

Variant 22-50229576-G-A is Benign according to our data. Variant chr22-50229576-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00315 (480/152268) while in subpopulation AFR AF= 0.0109 (453/41548). AF 95% confidence interval is 0.0101. There are 4 homozygotes in gnomad4. There are 241 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4 link	c.1118C>T	p.Pro373Leu	missense_variant, splice_region_variant	Exon 4 of 25	ENST00000248846.10	NP_065194.3	Q96RT7-1
TUBGCP6	XR_001755343.3 link	n.1682C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 20
TUBGCP6	XR_007067982.1 link	n.1682C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 19
TUBGCP6	XR_938347.3 link	n.1682C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TUBGCP6	ENST00000248846.10 link	c.1118C>T	p.Pro373Leu	missense_variant, splice_region_variant	Exon 4 of 25	1	NM_020461.4	ENSP00000248846.5	Q96RT7-1
TUBGCP6	ENST00000439308.6 link	c.1118C>T	p.Pro373Leu	missense_variant, splice_region_variant	Exon 4 of 25	1		ENSP00000397387.2	E7EQL8
TUBGCP6	ENST00000498611.5 link	n.1651C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 23	1
TUBGCP6	ENST00000434349.1 link	c.347C>T	p.Pro116Leu	missense_variant, splice_region_variant	Exon 3 of 6	5		ENSP00000409650.1	H7C358

Frequencies

GnomAD3 genomes

AF:

0.00315

AC:

480

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000832

AC:

166

AN:

199514

Hom.:

AF XY:

0.000584

AC XY:

AN XY:

107890

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.000470

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000135

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000700

Gnomad OTH exome

AF:

0.000195

GnomAD4 exome

AF:

0.000373

AC:

535

AN:

1433264

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

226

AN XY:

710682

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.000733

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.0000527

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000400

Gnomad4 OTH exome

AF:

0.000574

GnomAD4 genome

AF:

0.00315

AC:

480

AN:

152268

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000739

Hom.:

Bravo

AF:

0.00342

ESP6500AA

AF:

0.00957

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000830

AC:

100

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 24, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.3

DANN

Benign

0.79

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.62

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.75

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.052

Sift

Benign

0.38

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.017

B;.

Vest4

0.13

MVP

0.41

MPC

0.19

ClinPred

0.0023

GERP RS

0.47

Varity_R

0.028

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0

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

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