rs142798996

Positions:

chr22-50219736-G-A

Variant summary

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

The ENST00000248846.10(TUBGCP6):c.4223C>T(p.Ala1408Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,782 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1408S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 34)

Exomes 𝑓: 0.0013 ( 35 hom. )

Consequence

TUBGCP6
ENST00000248846.10 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.251

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=0.0038538873).

BP6

Variant 22-50219736-G-A is Benign according to our data. Variant chr22-50219736-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00198 (301/152342) while in subpopulation EAS AF= 0.0233 (121/5184). AF 95% confidence interval is 0.02. There are 4 homozygotes in gnomad4. There are 162 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TUBGCP6	NM_020461.4 linkuse as main transcript	c.4223C>T	p.Ala1408Val	missense_variant	18/25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3 linkuse as main transcript	n.4846C>T		non_coding_transcript_exon_variant	18/20
TUBGCP6	XR_007067982.1 linkuse as main transcript	n.3163C>T		non_coding_transcript_exon_variant	17/19
TUBGCP6	XR_938347.3 linkuse as main transcript	n.4787C>T		non_coding_transcript_exon_variant	18/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10 linkuse as main transcript	c.4223C>T	p.Ala1408Val	missense_variant	18/25	1	NM_020461.4	ENSP00000248846	P1	Q96RT7-1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

300

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00294

AC:

737

AN:

250858

Hom.:

AF XY:

0.00242

AC XY:

328

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.0100

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0178

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00135

AC:

1966

AN:

1461440

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

917

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0297

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152342

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

162

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0233

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.00267

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00252

AC:

306

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 20, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.27

DANN

Benign

0.80

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.31

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.071

Sift

Benign

0.24

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.81

P;.

Vest4

0.098

MVP

0.28

MPC

0.11

ClinPred

0.010

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.31

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