rs55985560

chr22-50218689-G-Achr22-50218689-G-C

Variant summary

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

The NM_020461.4(TUBGCP6):c.4821+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 1,613,450 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (5 hom., cov: 34)
  • Exomes 𝑓: 0.0095 (93 hom.)
• Consequence: TUBGCP6 NM_020461.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.714

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-50218689-G-A is Benign according to our data. Variant chr22-50218689-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 446010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50218689-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00675 (1028/152318) while in subpopulation NFE AF= 0.0112 (760/68014). AF 95% confidence interval is 0.0105. There are 5 homozygotes in gnomad4. There are 467 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP6	NM_020461.4	c.4821+14C>T		intron_variant		ENST00000248846.10
TUBGCP6	XR_938347.3	n.5378+21C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.4821+14C>T		intron_variant		1	NM_020461.4	P1

Frequencies

GnomAD3 genomes AF: 0.00677 AC: 1030 AN: 152200 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00709 AC: 1770 AN: 249526 Hom.: 14 AF XY: 0.00722 AC XY: 976 AN XY: 135090

Gnomad AFR exome AF: 0.00143

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00694

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.00837

GnomAD4 exome AF: 0.00951 AC: 13894 AN: 1461132 Hom.: 93 Cov.: 65 AF XY: 0.00929 AC XY: 6749 AN XY: 726860

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00246

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00687

Gnomad4 FIN exome AF: 0.0153

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.00878

GnomAD4 genome AF: 0.00675 AC: 1028 AN: 152318 Hom.: 5 Cov.: 34 AF XY: 0.00627 AC XY: 467 AN XY: 74472

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0111

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00466 Hom.: 0

Bravo AF: 0.00548

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 23, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 03, 2017	- -
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	-0.89
Cadd	Benign	0.22
Dann	Benign	0.56

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: rs55985560; hg19: chr22-50657118; COSMIC: COSV50549152; COSMIC: COSV50549152;