chr22-50220794-C-A

Variant names:

• chr22-50220794-C-A
• rs724159976
• NM_020461.4:c.3565G>T

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020461.4(TUBGCP6):​c.3565G>T​(p.Gly1189*) 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 NM_020461.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.82
• Publications: 3 publications found

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]

TUBGCP6 Gene-Disease associations (from GenCC):

• microcephaly and chorioretinopathy 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 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 VariationId is 162405.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.3565G>T	p.Gly1189*	stop_gained	Exon 16 of 25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.4129G>T		non_coding_transcript_exon_variant	Exon 16 of 20
TUBGCP6	XR_938347.3	n.4129G>T		non_coding_transcript_exon_variant	Exon 16 of 23
TUBGCP6	XR_007067982.1	n.3049-779G>T		intron_variant	Intron 15 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3565G>T	p.Gly1189*	stop_gained	Exon 16 of 25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.7	n.3565G>T		non_coding_transcript_exon_variant	Exon 16 of 25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.3617+481G>T		intron_variant	Intron 16 of 22	1
TUBGCP6	ENST00000491449.5	n.1872G>T		non_coding_transcript_exon_variant	Exon 8 of 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

Dec 01, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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
PhyloP100		2.8
Vest4		0.075
GERP RS		3.1
PromoterAI		-0.0016	Neutral
Mutation Taster		=2/198	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs724159976; hg19: chr22-50659223;