chr22-50218689-G-A

Variant names:

• chr22-50218689-G-A
• rs55985560
• NM_020461.4:c.4821+14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020461.4(TUBGCP6):​c.4821+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 1,613,450 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (5 hom., cov: 34)
  • Exomes 𝑓: 0.0095 (93 hom.)
• Consequence: TUBGCP6 NM_020461.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.714
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-50218689-G-A is Benign according to our data. Variant chr22-50218689-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00675 (1028/152318) while in subpopulation NFE AF = 0.0112 (760/68014). AF 95% confidence interval is 0.0105. There are 5 homozygotes in GnomAd4. There are 467 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.4821+14C>T		intron	N/A	NP_065194.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	ENST00000248846.10	TSL:1 MANE Select	c.4821+14C>T		intron	N/A	ENSP00000248846.5
	TUBGCP6	ENST00000425018.1	TSL:1	c.879+14C>T		intron	N/A	ENSP00000405979.1
	TUBGCP6	ENST00000439308.7	TSL:1	n.*398+14C>T		intron	N/A	ENSP00000397387.2

Frequencies

GnomAD3 genomes AF: 0.00677 AC: 1030 AN: 152200 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00709 AC: 1770 AN: 249526 AF XY: 0.00722

Gnomad AFR exome AF: 0.00143

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.00837

GnomAD4 exome AF: 0.00951 AC: 13894 AN: 1461132 Hom.: 93 Cov.: 65 AF XY: 0.00929 AC XY: 6749 AN XY: 726860

African (AFR) AF: 0.00149 AC: 50 AN: 33472

American (AMR) AF: 0.00246 AC: 110 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00687 AC: 592 AN: 86206

European-Finnish (FIN) AF: 0.0153 AC: 812 AN: 53144

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.0106 AC: 11753 AN: 1111710

Other (OTH) AF: 0.00878 AC: 530 AN: 60362

GnomAD4 genome AF: 0.00675 AC: 1028 AN: 152318 Hom.: 5 Cov.: 34 AF XY: 0.00627 AC XY: 467 AN XY: 74472

African (AFR) AF: 0.00159 AC: 66 AN: 41578

American (AMR) AF: 0.00255 AC: 39 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4824

European-Finnish (FIN) AF: 0.0111 AC: 118 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 760 AN: 68014

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00466 Hom.: 0

Bravo AF: 0.00548

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 23, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 03, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely 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	-0.89
CADD	Benign	0.22
DANN	Benign	0.56
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs55985560; hg19: chr22-50657118; COSMIC: COSV50549152; COSMIC: COSV50549152;