rs775586504

Variant names:

• chr10-133279863-C-A
• NM_006659.4:c.2612G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133279863-C-A
• chr10-133279863-C-T

Variant summary

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

The NM_006659.4(TUBGCP2):​c.2612G>T​(p.Arg871Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,752 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. R871H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TUBGCP2 NM_006659.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

Genes affected

TUBGCP2 (HGNC:18599): (tubulin gamma complex component 2) Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome and nucleoplasm. [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=0.18786716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP2	NM_006659.4	c.2612G>T	p.Arg871Leu	missense_variant	Exon 18 of 18	ENST00000252936.8	NP_006650.1
TUBGCP2	NM_001256617.2	c.2696G>T	p.Arg899Leu	missense_variant	Exon 19 of 19		NP_001243546.1
TUBGCP2	NM_001256618.2	c.2222G>T	p.Arg741Leu	missense_variant	Exon 17 of 17		NP_001243547.1
TUBGCP2	NR_046330.2	n.3332G>T		non_coding_transcript_exon_variant	Exon 18 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP2	ENST00000252936.8	c.2612G>T	p.Arg871Leu	missense_variant	Exon 18 of 18	2	NM_006659.4	ENSP00000252936.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454752 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723422

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: 0.0000193

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;.;.;T;T
Eigen	Benign	0.094
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	.;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;.;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.4	N;N;N;N;D
REVEL	Benign	0.094
Sift	Uncertain	0.0090	D;D;D;D;D
Sift4G	Uncertain	0.026	D;D;D;D;T
Polyphen		0.17	B;.;.;B;.
Vest4		0.25
MutPred		0.42		Loss of disorder (P = 0.0409);.;.;Loss of disorder (P = 0.0409);.;
MVP		0.49
MPC		0.55
ClinPred		0.79	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-135093367;