Genetic Variant NM_020461.4:c.4821+14C>T (chr22-50218689-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.714

Publications

2 publications found

Variant links:

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

TUBGCP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4 link	c.4821+14C>T		intron_variant	Intron 21 of 24	ENST00000248846.10	NP_065194.3	Q96RT7-1
TUBGCP6	XR_938347.3 link	n.5378+21C>T		intron_variant	Intron 21 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10 link	c.4821+14C>T		intron_variant	Intron 21 of 24	1	NM_020461.4	ENSP00000248846.5		Q96RT7-1

Frequencies

GnomAD3 genomes

AF:

0.00677

AC:

1030

AN:

152200

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00929

AC XY:

6749

AN XY:

726860

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

33472

American (AMR)

AF:

0.00246

AC:

110

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

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:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0106

AC:

11753

AN:

1111710

Other (OTH)

AF:

0.00878

AC:

530

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

942

1884

2826

3768

4710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

420

840

1260

1680

2100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00675

AC:

1028

AN:

152318

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

467

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41578

American (AMR)

AF:

0.00255

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00539

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0111

AC:

118

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

760

AN:

68014

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

109

164

218

273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00466

Hom.:

Bravo

AF:

0.00548

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.22

(source)

DANN

Benign

0.56

PhyloP100

-0.71

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over