rs1215314321

chr22-50220827-T-Achr22-50220827-T-Cchr22-50220827-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020461.4(TUBGCP6):c.3532A>T(p.Met1178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1178V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0290

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044837803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP6	NM_020461.4	c.3532A>T	p.Met1178Leu	missense_variant	16/25	ENST00000248846.10
TUBGCP6	XR_001755343.3	n.4096A>T		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.4096A>T		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3049-812A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3532A>T	p.Met1178Leu	missense_variant	16/25	1	NM_020461.4	P1
TUBGCP6	ENST00000439308.6	c.3532A>T	p.Met1178Leu	missense_variant	16/25	1
TUBGCP6	ENST00000498611.5	n.3617+448A>T		intron_variant, non_coding_transcript_variant		1
TUBGCP6	ENST00000491449.5	n.1839A>T		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4 AN: 84610 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000435

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.000225

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;AS_VQSR AF: 0.00 AC: 0 AN: 1289282 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 641220

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000590 AC: 5 AN: 84678 Hom.: 0 Cov.: 27 AF XY: 0.0000964 AC XY: 4 AN XY: 41498

Gnomad4 AFR AF: 0.0000455

Gnomad4 AMR AF: 0.000121

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000436

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.000225

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 26, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	1.8
Dann	Benign	0.65
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.059	T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.060	N;N
REVEL	Benign	0.015
Sift	Benign	0.38	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.0	B;.
Vest4		0.17
MutPred		0.32		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP		0.11
MPC		0.10
ClinPred		0.022	T
GERP RS		1.2
Varity_R		0.039
gMVP		0.19

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: rs1215314321; hg19: chr22-50659256;