22-50219182-G-A

Variant names:

• chr22-50219182-G-A
• rs17013240
• NM_020461.4:c.4512C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020461.4(TUBGCP6):​c.4512C>T​(p.Val1504Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 1,611,784 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (212 hom., cov: 34)
  • Exomes 𝑓: 0.0029 (191 hom.)
• Consequence: TUBGCP6 NM_020461.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.06
• Publications: 9 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), Orphanet, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-50219182-G-A is Benign according to our data. Variant chr22-50219182-G-A is described in ClinVar as Benign. ClinVar VariationId is 769166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	NM_020461.4	MANE Select	c.4512C>T	p.Val1504Val	synonymous	Exon 20 of 25	NP_065194.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	ENST00000248846.10	TSL:1 MANE Select	c.4512C>T	p.Val1504Val	synonymous	Exon 20 of 25	ENSP00000248846.5
	TUBGCP6	ENST00000425018.1	TSL:1	c.570C>T	p.Val190Val	synonymous	Exon 5 of 10	ENSP00000405979.1
	TUBGCP6	ENST00000439308.7	TSL:1	n.*89C>T		non_coding_transcript_exon	Exon 20 of 25	ENSP00000397387.2

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4574 AN: 152210 Hom.: 213 Cov.: 34

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00780 AC: 1937 AN: 248296 AF XY: 0.00567

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00528

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00362

GnomAD4 exome AF: 0.00290 AC: 4228 AN: 1459456 Hom.: 191 Cov.: 58 AF XY: 0.00244 AC XY: 1774 AN XY: 726128

African (AFR) AF: 0.102 AC: 3413 AN: 33478

American (AMR) AF: 0.00586 AC: 262 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51164

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5748

European-Non Finnish (NFE) AF: 0.000148 AC: 165 AN: 1111962

Other (OTH) AF: 0.00598 AC: 361 AN: 60362

GnomAD4 genome AF: 0.0301 AC: 4582 AN: 152328 Hom.: 212 Cov.: 34 AF XY: 0.0291 AC XY: 2167 AN XY: 74502

African (AFR) AF: 0.105 AC: 4366 AN: 41548

American (AMR) AF: 0.00986 AC: 151 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68036

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.00882 Hom.: 70

Bravo AF: 0.0345

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.027
DANN	Benign	0.86
PhyloP100		-1.1
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17013240; hg19: chr22-50657611;