15-22999743-T-C

Variant names:

• chr15-22999743-T-C
• rs1046860
• NM_052903.6:c.*77A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_052903.6(TUBGCP5):​c.*77A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,500,206 control chromosomes in the GnomAD database, including 13,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1817 hom., cov: 33)
  • Exomes 𝑓: 0.11 (11831 hom.)
• Consequence: TUBGCP5 NM_052903.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33

Genes affected

TUBGCP5 (HGNC:18600): (tubulin gamma complex component 5) Enables microtubule binding activity. Involved in microtubule nucleation. Located in centrosome and cytosol. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-22999743-T-C is Benign according to our data. Variant chr15-22999743-T-C is described in ClinVar as [Benign]. Clinvar id is 1270324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP5	NM_052903.6	c.*77A>G		3_prime_UTR_variant	Exon 23 of 23	ENST00000615383.5	NP_443135.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP5	ENST00000615383	c.*77A>G		3_prime_UTR_variant	Exon 23 of 23	1	NM_052903.6	ENSP00000480316.1
TUBGCP5	ENST00000614508.4	n.3028+826A>G		intron_variant	Intron 22 of 23	5		ENSP00000484566.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20454 AN: 151926 Hom.: 1813 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.114 AC: 153142 AN: 1348162 Hom.: 11831 Cov.: 19 AF XY: 0.112 AC XY: 76065 AN XY: 676244

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.0856

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.135 AC: 20477 AN: 152044 Hom.: 1817 Cov.: 33 AF XY: 0.136 AC XY: 10086 AN XY: 74336

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0717

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.0843

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.104

Alfa AF: 0.103 Hom.: 841

Bravo AF: 0.136

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	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

Other links and lift over

dbSNP: rs1046860; hg19: chr15-22873325;