rs17013240

chr22-50219182-G-Achr22-50219182-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020461.4(TUBGCP6):c.4512C>T(p.Val1504=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 1,611,784 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (212 hom., cov: 34)
  • Exomes 𝑓: 0.0029 (191 hom.)
• Consequence: TUBGCP6 NM_020461.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-50219182-G-A is Benign according to our data. Variant chr22-50219182-G-A is described in ClinVar as [Benign]. Clinvar id is 769166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50219182-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP6	NM_020461.4	c.4512C>T	p.Val1504=	synonymous_variant	20/25	ENST00000248846.10
TUBGCP6	XR_001755343.3	n.5135C>T		non_coding_transcript_exon_variant	20/20
TUBGCP6	XR_007067982.1	n.3452C>T		non_coding_transcript_exon_variant	19/19
TUBGCP6	XR_938347.3	n.5076C>T		non_coding_transcript_exon_variant	20/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.4512C>T	p.Val1504=	synonymous_variant	20/25	1	NM_020461.4	P1

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4574 AN: 152210 Hom.: 213 Cov.: 34

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.00780 AC: 1937 AN: 248296 Hom.: 91 AF XY: 0.00567 AC XY: 763 AN XY: 134564

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00528

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00362

GnomAD4 exome AF: 0.00290 AC: 4228 AN: 1459456 Hom.: 191 Cov.: 58 AF XY: 0.00244 AC XY: 1774 AN XY: 726128

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.00586

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.00598

GnomAD4 genome AF: 0.0301 AC: 4582 AN: 152328 Hom.: 212 Cov.: 34 AF XY: 0.0291 AC XY: 2167 AN XY: 74502

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.00986

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.00531 Hom.: 37

Bravo AF: 0.0345

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.027
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs17013240; hg19: chr22-50657611;