rs1198223386

Variant names:

• chr15-23005503-G-C
• NM_052903.6:c.2641C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-23005503-G-C
• chr15-23005503-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052903.6(TUBGCP5):​c.2641C>G​(p.His881Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. H881N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TUBGCP5 NM_052903.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.19

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP5	NM_052903.6	c.2641C>G	p.His881Asp	missense_variant	Exon 19 of 23	ENST00000615383.5	NP_443135.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP5	ENST00000615383.5	c.2641C>G	p.His881Asp	missense_variant	Exon 19 of 23	1	NM_052903.6	ENSP00000480316.1
TUBGCP5	ENST00000620435.4	c.2641C>G	p.His881Asp	missense_variant	Exon 19 of 22	2		ENSP00000481853.1
TUBGCP5	ENST00000610294.1	c.604C>G	p.His202Asp	missense_variant	Exon 5 of 5	5		ENSP00000483015.1
TUBGCP5	ENST00000614508.4	n.2641C>G		non_coding_transcript_exon_variant	Exon 19 of 24	5		ENSP00000484566.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.
LIST_S2	Uncertain	0.92	D;D
MetaRNN	Pathogenic	0.87	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.97
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-22867565;