15-23003304-T-C

Variant names:

• chr15-23003304-T-C
• rs2289814
• NM_052903.6:c.2839-151A>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.2839-151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 659,072 control chromosomes in the GnomAD database, including 6,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (1068 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5245 hom.)
• Consequence: TUBGCP5 NM_052903.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00300

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=-0.88).
• BP6: Variant 15-23003304-T-C is Benign according to our data. Variant chr15-23003304-T-C is described in ClinVar as [Benign]. Clinvar id is 1258357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP5	NM_052903.6	c.2839-151A>G		intron_variant	Intron 20 of 22	ENST00000615383.5	NP_443135.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP5	ENST00000615383.5	c.2839-151A>G		intron_variant	Intron 20 of 22	1	NM_052903.6	ENSP00000480316.1
TUBGCP5	ENST00000620435.4	c.2839-151A>G		intron_variant	Intron 20 of 21	2		ENSP00000481853.1
TUBGCP5	ENST00000614508.4	n.2839-151A>G		intron_variant	Intron 20 of 23	5		ENSP00000484566.1
TUBGCP5	ENST00000620238.1	n.470-151A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13506 AN: 152094 Hom.: 1068 Cov.: 32

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.107 AC: 53987 AN: 506860 Hom.: 5245 AF XY: 0.105 AC XY: 27915 AN XY: 265372

Gnomad4 AFR exome AF: 0.0386

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.0752

Gnomad4 FIN exome AF: 0.0818

Gnomad4 NFE exome AF: 0.0885

Gnomad4 OTH exome AF: 0.0998

GnomAD4 genome AF: 0.0888 AC: 13510 AN: 152212 Hom.: 1068 Cov.: 32 AF XY: 0.0903 AC XY: 6718 AN XY: 74416

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.0547

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.0926

Gnomad4 NFE AF: 0.0958

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0486 Hom.: 56

Bravo AF: 0.0858

Asia WGS AF: 0.222 AC: 772 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	-0.88
CADD	Benign	0.47
DANN	Benign	0.47

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: rs2289814; hg19: chr15-22869764;