NM_052903.6:c.2180T>G

Variant names:

• chr15-23008846-A-C
• rs1555436162
• NM_052903.6:c.2180T>G

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.2180T>G​(p.Phe727Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBGCP5 NM_052903.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.46
• Publications: 2 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, 0.887

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.2180T>G	p.Phe727Cys	missense	Exon 16 of 23	NP_443135.3
	TUBGCP5	NM_001354372.2		c.2183T>G	p.Phe728Cys	missense	Exon 16 of 23	NP_001341301.1
	TUBGCP5	NM_001354373.2		c.2180T>G	p.Phe727Cys	missense	Exon 16 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.2180T>G	p.Phe727Cys	missense	Exon 16 of 23	ENSP00000480316.1	Q96RT8-1
	TUBGCP5	ENST00000620435.4	TSL:2	c.2180T>G	p.Phe727Cys	missense	Exon 16 of 22	ENSP00000481853.1	Q96RT8-2
	TUBGCP5	ENST00000959740.1		c.2156T>G	p.Phe719Cys	missense	Exon 16 of 23	ENSP00000629799.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Microcephaly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
LIST_S2	Uncertain	0.93	D
MetaRNN	Pathogenic	0.89	D
PhyloP100		8.5
Sift4G	Uncertain	0.0020	D
Vest4		0.94
PromoterAI		-0.00010	Neutral
gMVP		0.98

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: rs1555436162; hg19: chr15-22864222;