chr22-50227980-C-A

Position:

• chr22-50227980-C-A

Variant summary

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

The NM_020461.4(TUBGCP6):​c.1339G>T​(p.Val447Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,220 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. Synonymous variant affecting the same amino acid position (i.e. V447V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 (HGNC:):

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, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.1339G>T	p.Val447Phe	missense_variant	5/25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.1903G>T		non_coding_transcript_exon_variant	5/20
TUBGCP6	XR_007067982.1	n.1903G>T		non_coding_transcript_exon_variant	5/19
TUBGCP6	XR_938347.3	n.1903G>T		non_coding_transcript_exon_variant	5/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.1339G>T	p.Val447Phe	missense_variant	5/25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.6	c.1339G>T	p.Val447Phe	missense_variant	5/25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.1872G>T		non_coding_transcript_exon_variant	5/23	1
TUBGCP6	ENST00000434349.1	c.568G>T	p.Val190Phe	missense_variant	4/6	5		ENSP00000409650.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1418828 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701376

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 AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74366

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.92
MutPred		0.67		Gain of glycosylation at P452 (P = 0.2071);Gain of glycosylation at P452 (P = 0.2071);
MVP		0.52
MPC		0.61
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.39
gMVP		0.80

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: rs182347943; hg19: chr22-50666409;