rs9628306

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-50220869-C-A
• chr22-50220869-C-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), ClinGen, G2P, Orphanet

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020461.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	NM_020461.4	MANE Select	c.3490G>T	p.Val1164Leu	missense	Exon 16 of 25	NP_065194.3	Q96RT7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	ENST00000248846.10	TSL:1 MANE Select	c.3490G>T	p.Val1164Leu	missense	Exon 16 of 25	ENSP00000248846.5	Q96RT7-1
	TUBGCP6	ENST00000439308.7	TSL:1	n.3490G>T		non_coding_transcript_exon	Exon 16 of 25	ENSP00000397387.2	E7EQL8
	TUBGCP6	ENST00000498611.5	TSL:1	n.3617+406G>T		intron	N/A

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 v4.9

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
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.61
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.068
Sift	Benign	0.18	T
Sift4G	Benign	0.13	T
Polyphen		0.68	P
Vest4		0.40
MutPred		0.45		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;