22-50220869-C-A

Variant names:

• chr22-50220869-C-A
• rs9628306
• NM_020461.4:c.3490G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020461.4(TUBGCP6):​c.3490G>T​(p.Val1164Leu) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1164M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17273256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.3490G>T	p.Val1164Leu	missense_variant	Exon 16 of 25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.4054G>T		non_coding_transcript_exon_variant	Exon 16 of 20
TUBGCP6	XR_938347.3	n.4054G>T		non_coding_transcript_exon_variant	Exon 16 of 23
TUBGCP6	XR_007067982.1	n.3049-854G>T		intron_variant	Intron 15 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3490G>T	p.Val1164Leu	missense_variant	Exon 16 of 25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.7	n.3490G>T		non_coding_transcript_exon_variant	Exon 16 of 25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.3617+406G>T		intron_variant	Intron 16 of 22	1
TUBGCP6	ENST00000491449.5	n.1797G>T		non_coding_transcript_exon_variant	Exon 8 of 16	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.81	T;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
PhyloP100		0.61
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.068
Sift	Benign	0.18	T;D
Sift4G	Benign	0.13	T;T
Polyphen		0.68	P;.
Vest4		0.40
MutPred		0.45		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.30
MPC		0.10
ClinPred		0.47	T
GERP RS		4.6
PromoterAI		-0.030	Neutral
Varity_R		0.051
gMVP		0.30
Mutation Taster		=94/6	polymorphism

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: rs9628306; hg19: chr22-50659298;