chr22-50233406-C-T

Variant names:

• chr22-50233406-C-T
• rs141805017
• NM_020461.4:c.1026G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6 BP7 BS1

The NM_020461.4(TUBGCP6):​c.1026G>A​(p.Pro342Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,613,920 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00052 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: TUBGCP6 NM_020461.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -4.22

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 Benign. Variant got -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 22-50233406-C-T is Benign according to our data. Variant chr22-50233406-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212503.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-4.22 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000519 (79/152316) while in subpopulation NFE AF= 0.000941 (64/68006). AF 95% confidence interval is 0.000756. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.1026G>A	p.Pro342Pro	synonymous_variant	Exon 3 of 25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.1590G>A		non_coding_transcript_exon_variant	Exon 3 of 20
TUBGCP6	XR_007067982.1	n.1590G>A		non_coding_transcript_exon_variant	Exon 3 of 19
TUBGCP6	XR_938347.3	n.1590G>A		non_coding_transcript_exon_variant	Exon 3 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.1026G>A	p.Pro342Pro	synonymous_variant	Exon 3 of 25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.6	c.1026G>A	p.Pro342Pro	synonymous_variant	Exon 3 of 25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.1559G>A		non_coding_transcript_exon_variant	Exon 3 of 23	1
TUBGCP6	ENST00000434349.1	c.255G>A	p.Pro85Pro	synonymous_variant	Exon 2 of 6	5		ENSP00000409650.1

Frequencies

GnomAD3 genomes AF: 0.000519 AC: 79 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000455 AC: 114 AN: 250514 Hom.: 0 AF XY: 0.000317 AC XY: 43 AN XY: 135526

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.000769

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000342 AC: 500 AN: 1461604 Hom.: 1 Cov.: 32 AF XY: 0.000373 AC XY: 271 AN XY: 727102

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000769

Gnomad4 NFE exome AF: 0.000383

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.000519 AC: 79 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29 AN XY: 74462

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000671 Hom.: 0

Bravo AF: 0.000366

EpiCase AF: 0.000600

EpiControl AF: 0.000534

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:3

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TUBGCP6: BP4, BP7 -

May 29, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Uncertain:1

Feb 12, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.63
DANN	Benign	0.76

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: rs141805017; hg19: chr22-50671835; COSMIC: COSV50593705;