rs137934849

Positions:

Variant summary

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

The NM_020461.4(TUBGCP6):c.655G>T(p.Val219Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000424 in 1,613,680 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 5.65

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:

TUBGCP6 (HGNC:):

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=0.015889406).

BP6

Variant 22-50243805-C-A is Benign according to our data. Variant chr22-50243805-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 437161.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000423 (618/1461440) while in subpopulation MID AF= 0.00364 (21/5766). AF 95% confidence interval is 0.00244. There are 1 homozygotes in gnomad4_exome. There are 325 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4 linkuse as main transcript	c.655G>T	p.Val219Leu	missense_variant	1/25	ENST00000248846.10	NP_065194.3	Q96RT7-1
TUBGCP6	XR_001755343.3 linkuse as main transcript	n.1219G>T		non_coding_transcript_exon_variant	1/20
TUBGCP6	XR_007067982.1 linkuse as main transcript	n.1219G>T		non_coding_transcript_exon_variant	1/19
TUBGCP6	XR_938347.3 linkuse as main transcript	n.1219G>T		non_coding_transcript_exon_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TUBGCP6	ENST00000248846.10 linkuse as main transcript	c.655G>T	p.Val219Leu	missense_variant	1/25	1	NM_020461.4	ENSP00000248846.5	Q96RT7-1
TUBGCP6	ENST00000439308.6 linkuse as main transcript	c.655G>T	p.Val219Leu	missense_variant	1/25	1		ENSP00000397387.2	E7EQL8
TUBGCP6	ENST00000498611.5 linkuse as main transcript	n.1188G>T		non_coding_transcript_exon_variant	1/23	1

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000602

AC:

151

AN:

250746

Hom.:

AF XY:

0.000582

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00408

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000662

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000423

AC:

618

AN:

1461440

Hom.:

Cov.:

AF XY:

0.000447

AC XY:

325

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00509

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.000264

Gnomad4 NFE exome

AF:

0.000330

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.000434

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000615

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000478

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000533

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

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

May 05, 2016

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

TUBGCP6-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2022

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.18

Sift

Benign

0.037

D;D

Sift4G

Benign

0.067

T;T

Polyphen

1.0

D;.

Vest4

0.30

MutPred

0.32

Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);

MVP

0.44

MPC

0.52

ClinPred

0.085

GERP RS

4.2

Varity_R

0.30

gMVP

0.28

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