15-23000614-C-G

Variant names:

• chr15-23000614-C-G
• rs2064315646
• NM_052903.6:c.2983G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_052903.6(TUBGCP5):​c.2983G>C​(p.Val995Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TUBGCP5 NM_052903.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.21
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.805

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052903.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP5	NM_052903.6	MANE Select	c.2983G>C	p.Val995Leu	missense	Exon 22 of 23	NP_443135.3
	TUBGCP5	NM_001354372.2		c.2986G>C	p.Val996Leu	missense	Exon 22 of 23	NP_001341301.1
	TUBGCP5	NM_001354373.2		c.2983G>C	p.Val995Leu	missense	Exon 22 of 23	NP_001341302.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP5	ENST00000615383.5	TSL:1 MANE Select	c.2983G>C	p.Val995Leu	missense	Exon 22 of 23	ENSP00000480316.1	Q96RT8-1
	TUBGCP5	ENST00000620435.4	TSL:2	c.2983G>C	p.Val995Leu	missense	Exon 22 of 22	ENSP00000481853.1	Q96RT8-2
	TUBGCP5	ENST00000959740.1		c.2959G>C	p.Val987Leu	missense	Exon 22 of 23	ENSP00000629799.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458208 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725484

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.0000225 AC: 1 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109370

Other (OTH) AF: 0.00 AC: 0 AN: 60284

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
LIST_S2	Uncertain	0.94	D
MetaRNN	Pathogenic	0.81	D
PhyloP100		7.2
Sift4G	Uncertain	0.058	T
Vest4		0.87
gMVP		0.96

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

Other links and lift over

dbSNP: rs2064315646; hg19: chr15-22872454;