chr22-50220794-C-A

Position:

• chr22-50220794-C-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The ENST00000248846.10(TUBGCP6):​c.3565G>T​(p.Gly1189Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBGCP6 ENST00000248846.10 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.82

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-50220794-C-A is Pathogenic according to our data. Variant chr22-50220794-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 162405.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-50220794-C-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.3565G>T	p.Gly1189Ter	stop_gained	16/25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.4129G>T		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.4129G>T		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3049-779G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3565G>T	p.Gly1189Ter	stop_gained	16/25	1	NM_020461.4	ENSP00000248846	P1
TUBGCP6	ENST00000439308.6	c.3565G>T	p.Gly1189Ter	stop_gained	16/25	1		ENSP00000397387
TUBGCP6	ENST00000498611.5	n.3617+481G>T		intron_variant, non_coding_transcript_variant		1
TUBGCP6	ENST00000491449.5	n.1872G>T		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Microcephaly and chorioretinopathy 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	33
DANN	Benign	0.97
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.0090
FATHMM_MKL	Uncertain	0.88	D
MutationTaster	Benign	1.0	A;A
Vest4		0.075
GERP RS		3.1

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: rs724159976; hg19: chr22-50659223;