rs149152116

Positions:

• chr22-50218218-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000425018.1(TUBGCP6):​c.1165C>T​(p.Arg389Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,612,482 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 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. R389H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (11 hom.)
• Consequence: TUBGCP6 ENST00000425018.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.308

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009924054).
• BP6: Variant 22-50218218-G-A is Benign according to our data. Variant chr22-50218218-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 437142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50218218-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00204 (311/152320) while in subpopulation NFE AF= 0.00347 (236/68020). AF 95% confidence interval is 0.00311. There are 2 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.5139C>T	p.His1713His	synonymous_variant	23/25	ENST00000248846.10	NP_065194.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.5139C>T	p.His1713His	synonymous_variant	23/25	1	NM_020461.4	ENSP00000248846.5

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 311 AN: 152202 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00210 AC: 523 AN: 249006 Hom.: 0 AF XY: 0.00217 AC XY: 293 AN XY: 135040

Gnomad AFR exome AF: 0.000870

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00216

Gnomad FIN exome AF: 0.000380

Gnomad NFE exome AF: 0.00329

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00325 AC: 4743 AN: 1460162 Hom.: 11 Cov.: 37 AF XY: 0.00319 AC XY: 2318 AN XY: 726422

Gnomad4 AFR exome AF: 0.000807

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00194

Gnomad4 FIN exome AF: 0.000385

Gnomad4 NFE exome AF: 0.00387

Gnomad4 OTH exome AF: 0.00239

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152320 Hom.: 2 Cov.: 33 AF XY: 0.00191 AC XY: 142 AN XY: 74480

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00347

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00266 Hom.: 0

Bravo AF: 0.00210

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00477 AC: 41

ExAC AF: 0.00200 AC: 243

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00387

EpiControl AF: 0.00314

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 02, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	TUBGCP6: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 16, 2018

- -

Microcephaly and chorioretinopathy 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Jun 28, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.016
DANN	Benign	0.90
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0099	T
MetaSVM	Benign	-0.75	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.022	D
MVP		0.072
ClinPred		0.027	T
GERP RS		-7.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs149152116; hg19: chr22-50656647;