22-50217697-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020461.4(TUBGCP6):c.*39C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,589,640 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00064 (11 hom.)
• Consequence: TUBGCP6 NM_020461.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.27

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-50217697-G-A is Benign according to our data. Variant chr22-50217697-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1214732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00638 (971/152210) while in subpopulation AFR AF= 0.0218 (904/41492). AF 95% confidence interval is 0.0206. There are 13 homozygotes in gnomad4. There are 472 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP6	NM_020461.4	c.*39C>T		3_prime_UTR_variant	25/25	ENST00000248846.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.*39C>T		3_prime_UTR_variant	25/25	1	NM_020461.4	P1

Frequencies

GnomAD3 genomes AF: 0.00636 AC: 968 AN: 152092 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00146 AC: 341 AN: 234244 Hom.: 5 AF XY: 0.00109 AC XY: 138 AN XY: 126536

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.000797

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000698

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000571

Gnomad OTH exome AF: 0.000524

GnomAD4 exome AF: 0.000639 AC: 919 AN: 1437430 Hom.: 11 Cov.: 30 AF XY: 0.000554 AC XY: 396 AN XY: 714178

Gnomad4 AFR exome AF: 0.0201

Gnomad4 AMR exome AF: 0.000976

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000763

Gnomad4 SAS exome AF: 0.0000474

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000932

Gnomad4 OTH exome AF: 0.00165

GnomAD4 genome AF: 0.00638 AC: 971 AN: 152210 Hom.: 13 Cov.: 33 AF XY: 0.00634 AC XY: 472 AN XY: 74414

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00282 Hom.: 0

Bravo AF: 0.00697

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.33
Dann	Benign	0.61

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: rs9628305; hg19: chr22-50656126;