rs797046079

chr22-50221466-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020461.4(TUBGCP6):c.2893C>T(p.Pro965Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P965L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.318

Genes affected

TUBGCP6 (HGNC:18127): (tubulin gamma complex component 6) The protein encoded by this gene is part of a large multisubunit complex required for microtubule nucleation at the centrosome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05788192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP6	NM_020461.4	c.2893C>T	p.Pro965Ser	missense_variant	16/25	ENST00000248846.10
TUBGCP6	XR_001755343.3	n.3457C>T		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.3457C>T		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3048+562C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.2893C>T	p.Pro965Ser	missense_variant	16/25	1	NM_020461.4	P1
TUBGCP6	ENST00000439308.6	c.2893C>T	p.Pro965Ser	missense_variant	16/25	1
TUBGCP6	ENST00000498611.5	n.3426C>T		non_coding_transcript_exon_variant	16/23	1
TUBGCP6	ENST00000491449.5	n.1200C>T		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1440966 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 715714

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 24, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	5.9
Dann	Benign	0.58
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.64	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.36	N;N
REVEL	Benign	0.028
Sift	Benign	0.77	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.030	B;.
Vest4		0.036
MutPred		0.36		Gain of glycosylation at P965 (P = 0.0416);Gain of glycosylation at P965 (P = 0.0416);
MVP		0.24
MPC		0.11
ClinPred		0.029	T
GERP RS		1.5
Varity_R		0.024
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs797046079; hg19: chr22-50659895; COSMIC: COSV105066199; COSMIC: COSV105066199;