15-22999831-C-G

Variant names:

• chr15-22999831-C-G
• rs1030924037
• NM_052903.6:c.3064G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052903.6(TUBGCP5):​c.3064G>C​(p.Glu1022Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E1022K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: TUBGCP5 NM_052903.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.02
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26314905).

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.3064G>C	p.Glu1022Gln	missense	Exon 23 of 23	NP_443135.3
	TUBGCP5	NM_001354377.2		c.3067G>C	p.Glu1023Gln	missense	Exon 23 of 23	NP_001341306.1
	TUBGCP5	NM_001354372.2		c.3031+738G>C		intron	N/A	NP_001341301.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP5	ENST00000615383.5	TSL:1 MANE Select	c.3064G>C	p.Glu1022Gln	missense	Exon 23 of 23	ENSP00000480316.1	Q96RT8-1
	TUBGCP5	ENST00000959740.1		c.3040G>C	p.Glu1014Gln	missense	Exon 23 of 23	ENSP00000629799.1
	TUBGCP5	ENST00000939427.1		c.3013G>C	p.Glu1005Gln	missense	Exon 23 of 23	ENSP00000609486.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461604 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111784

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_noAF	Pathogenic	0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.26	T
PhyloP100		7.0
Sift4G	Pathogenic	0.0	D
Vest4		0.39
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1030924037; hg19: chr15-22873237;