rs139974572

Positions:

• chr22-50244299-G-A
• chr22-50244299-G-C

Variant summary

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

The NM_020461.4(TUBGCP6):​c.161C>T​(p.Thr54Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T54S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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]

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=0.06991845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP6	NM_020461.4	c.161C>T	p.Thr54Ile	missense_variant	1/25	ENST00000248846.10
TUBGCP6	XR_001755343.3	n.725C>T		non_coding_transcript_exon_variant	1/20
TUBGCP6	XR_007067982.1	n.725C>T		non_coding_transcript_exon_variant	1/19
TUBGCP6	XR_938347.3	n.725C>T		non_coding_transcript_exon_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.161C>T	p.Thr54Ile	missense_variant	1/25	1	NM_020461.4	P1
TUBGCP6	ENST00000439308.6	c.161C>T	p.Thr54Ile	missense_variant	1/25	1
TUBGCP6	ENST00000498611.5	n.694C>T		non_coding_transcript_exon_variant	1/23	1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461286 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726912

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: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74386

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.17
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.63	P;.
Vest4		0.070
MutPred		0.22		Gain of helix (P = 0.027);Gain of helix (P = 0.027);
MVP		0.28
MPC		0.11
ClinPred		0.24	T
GERP RS		-1.2
Varity_R		0.050
gMVP		0.24

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: rs139974572; hg19: chr22-50682728;