15-22999824-C-T

Variant names:

• chr15-22999824-C-T
• NM_052903.6:c.3071G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052903.6(TUBGCP5):​c.3071G>A​(p.Ser1024Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TUBGCP5 NM_052903.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09449631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP5	NM_052903.6	c.3071G>A	p.Ser1024Asn	missense_variant	Exon 23 of 23	ENST00000615383.5	NP_443135.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP5	ENST00000615383.5	c.3071G>A	p.Ser1024Asn	missense_variant	Exon 23 of 23	1	NM_052903.6	ENSP00000480316.1
TUBGCP5	ENST00000614508.4	n.3028+745G>A		intron_variant	Intron 22 of 23	5		ENSP00000484566.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3071G>A (p.S1024N) alteration is located in exon 23 (coding exon 23) of the TUBGCP5 gene. This alteration results from a G to A substitution at nucleotide position 3071, causing the serine (S) at amino acid position 1024 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Pathogenic	0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.094	T
Sift4G	Uncertain	0.017	D
Vest4		0.13
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-22873244;