15-23003072-T-G

Variant names:

• chr15-23003072-T-G
• rs149154554
• NM_052903.6:c.2920A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052903.6(TUBGCP5):​c.2920A>C​(p.Thr974Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T974A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBGCP5 NM_052903.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28890717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP5	NM_052903.6	c.2920A>C	p.Thr974Pro	missense_variant	Exon 21 of 23	ENST00000615383.5	NP_443135.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP5	ENST00000615383.5	c.2920A>C	p.Thr974Pro	missense_variant	Exon 21 of 23	1	NM_052903.6	ENSP00000480316.1
TUBGCP5	ENST00000620435.4	c.2920A>C	p.Thr974Pro	missense_variant	Exon 21 of 22	2		ENSP00000481853.1
TUBGCP5	ENST00000614508.4	n.2920A>C		non_coding_transcript_exon_variant	Exon 21 of 24	5		ENSP00000484566.1
TUBGCP5	ENST00000620238.1	n.*19A>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.00410

EpiControl AF: 0.00462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.045	T;.
LIST_S2	Benign	0.79	T;T
MetaRNN	Benign	0.29	T;T
Sift4G	Uncertain	0.045	D;D
Vest4		0.25
gMVP		0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149154554; hg19: chr15-22869996;