chr22-50220977-T-G

Position:

• chr22-50220977-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_020461.4(TUBGCP6):​c.3382A>C​(p.Arg1128Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBGCP6 NM_020461.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.0710

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-50220977-T-G is Benign according to our data. Variant chr22-50220977-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 437149.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-0.071 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.3382A>C	p.Arg1128Arg	synonymous_variant	16/25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.3946A>C		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.3946A>C		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3049-962A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3382A>C	p.Arg1128Arg	synonymous_variant	16/25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.6	c.3382A>C	p.Arg1128Arg	synonymous_variant	16/25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.3617+298A>C		intron_variant		1
TUBGCP6	ENST00000491449.5	n.1689A>C		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 272 AN: 103018 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00354

Gnomad AMI AF: 0.00890

Gnomad AMR AF: 0.00320

Gnomad ASJ AF: 0.00235

Gnomad EAS AF: 0.00241

Gnomad SAS AF: 0.00129

Gnomad FIN AF: 0.00183

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.00418

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000111 AC: 16 AN: 1435400 Hom.: 0 Cov.: 37 AF XY: 0.00000700 AC XY: 5 AN XY: 714454

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000120

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000130

Gnomad4 SAS exome AF: 0.0000354

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000274

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00267 AC: 275 AN: 103084 Hom.: 0 Cov.: 32 AF XY: 0.00227 AC XY: 115 AN XY: 50688

Gnomad4 AFR AF: 0.00357

Gnomad4 AMR AF: 0.00330

Gnomad4 ASJ AF: 0.00235

Gnomad4 EAS AF: 0.00272

Gnomad4 SAS AF: 0.00129

Gnomad4 FIN AF: 0.00183

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.00415

Alfa AF: 0.0386 Hom.: 0

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 11, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	TUBGCP6: BP4, BP7 -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.42

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: rs1266725037; hg19: chr22-50659406; COSMIC: COSV50537528; COSMIC: COSV50537528;