22-50220708-A-T

Position:

• chr22-50220708-A-T

Variant summary

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

The NM_020461.4(TUBGCP6):​c.3651T>A​(p.His1217Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22912472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.3651T>A	p.His1217Gln	missense_variant	16/25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.4215T>A		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.4215T>A		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3049-693T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3651T>A	p.His1217Gln	missense_variant	16/25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.6	c.3651T>A	p.His1217Gln	missense_variant	16/25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.3617+567T>A		intron_variant		1
TUBGCP6	ENST00000491449.5	n.1958T>A		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251084 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457166 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 725066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

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.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	2.4
DANN	Benign	0.79
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.029	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;.
Vest4		0.22
MutPred		0.49		Gain of MoRF binding (P = 0.0785);Gain of MoRF binding (P = 0.0785);
MVP		0.47
MPC		0.30
ClinPred		0.38	T
GERP RS		-8.9
Varity_R		0.046
gMVP		0.55

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: rs148914897; hg19: chr22-50659137;