15-23000647-C-T

Variant names:

• chr15-23000647-C-T
• rs762338302
• NM_052903.6:c.2950G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052903.6(TUBGCP5):​c.2950G>A​(p.Glu984Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,304 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: 0.0000014 (0 hom.)
• Consequence: TUBGCP5 NM_052903.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.21
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

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.2950G>A	p.Glu984Lys	missense	Exon 22 of 23	NP_443135.3
	TUBGCP5	NM_001354372.2		c.2953G>A	p.Glu985Lys	missense	Exon 22 of 23	NP_001341301.1
	TUBGCP5	NM_001354373.2		c.2950G>A	p.Glu984Lys	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.2950G>A	p.Glu984Lys	missense	Exon 22 of 23	ENSP00000480316.1	Q96RT8-1
	TUBGCP5	ENST00000620435.4	TSL:2	c.2950G>A	p.Glu984Lys	missense	Exon 22 of 22	ENSP00000481853.1	Q96RT8-2
	TUBGCP5	ENST00000959740.1		c.2926G>A	p.Glu976Lys	missense	Exon 22 of 23	ENSP00000629799.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248758 AF XY: 0.00000743

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453304 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 723306

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.0000226 AC: 1 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106002

Other (OTH) AF: 0.00 AC: 0 AN: 60106

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.93
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T
LIST_S2	Uncertain	0.97	D
MetaRNN	Pathogenic	0.87	D
PhyloP100		7.2
Sift4G	Pathogenic	0.0	D
Vest4		0.95
gMVP		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762338302; hg19: chr15-22872421;