22-50220869-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The NM_020461.4(TUBGCP6):c.3490G>A(p.Val1164Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,611,396 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1164A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.610

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 -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007892489).

BP6

Variant 22-50220869-C-T is Benign according to our data. Variant chr22-50220869-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 437147.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00143 (216/150576) while in subpopulation AFR AF= 0.00509 (208/40864). AF 95% confidence interval is 0.00452. There are 0 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TUBGCP6	NM_020461.4 linkuse as main transcript	c.3490G>A	p.Val1164Met	missense_variant	16/25	ENST00000248846.10
TUBGCP6	XR_001755343.3 linkuse as main transcript	n.4054G>A		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3 linkuse as main transcript	n.4054G>A		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1 linkuse as main transcript	n.3049-854G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP6	ENST00000248846.10 linkuse as main transcript	c.3490G>A	p.Val1164Met	missense_variant	16/25	1	NM_020461.4	P1	Q96RT7-1
TUBGCP6	ENST00000439308.6 linkuse as main transcript	c.3490G>A	p.Val1164Met	missense_variant	16/25	1
TUBGCP6	ENST00000498611.5 linkuse as main transcript	n.3617+406G>A		intron_variant, non_coding_transcript_variant		1
TUBGCP6	ENST00000491449.5 linkuse as main transcript	n.1797G>A		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

215

AN:

150450

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

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:

0.0000739

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000314

AC:

AN:

251420

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000197

AC:

288

AN:

1460820

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

726716

show subpopulations

Gnomad4 AFR exome

AF:

0.00634

Gnomad4 AMR exome

AF:

0.0000898

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.00143

AC:

216

AN:

150576

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

73594

show subpopulations

Gnomad4 AFR

AF:

0.00509

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000739

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000645

Hom.:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 24, 2016

- -

TUBGCP6-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 21, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.

Eigen

Benign

-0.046

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.0079

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.053

Sift

Benign

0.056

T;D

Sift4G

Uncertain

0.043

D;T

Polyphen

0.82

P;.

Vest4

0.42

MVP

0.31

MPC

0.11

ClinPred

0.032

GERP RS

4.6

Varity_R

0.038

gMVP

0.29

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

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