Genetic Variant TUBGCP6:c.2270+701A>G (chr22-50223440-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020461.4(TUBGCP6):c.2270+701A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,634 control chromosomes in the GnomAD database, including 49,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 49691 hom., cov: 33)

Exomes 𝑓: 0.74 ( 132 hom. )

Consequence

TUBGCP6
NM_020461.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.401

Publications

15 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), ClinGen, G2P, Orphanet

TUBGCP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	NM_020461.4	MANE Select	c.2270+701A>G		intron	N/A	NP_065194.3	Q96RT7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TUBGCP6	ENST00000248846.10	TSL:1 MANE Select	c.2270+701A>G	intron	N/A	ENSP00000248846.5	Q96RT7-1
TUBGCP6	ENST00000439308.7	TSL:1	n.2270+701A>G	intron	N/A	ENSP00000397387.2	E7EQL8
TUBGCP6	ENST00000489511.5	TSL:1	n.287+701A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.802

AC:

121952

AN:

152052

Hom.:

49640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.947

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.706

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.878

Gnomad FIN

AF:

0.790

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.738

Gnomad OTH

AF:

0.776

GnomAD4 exome

AF:

0.737

AC:

342

AN:

464

Hom.:

132

Cov.:

AF XY:

0.765

AC XY:

208

AN XY:

272

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.571

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.700

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.739

AC:

281

AN:

380

Other (OTH)

AF:

0.792

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.802

AC:

122052

AN:

152170

Hom.:

49691

Cov.:

AF XY:

0.806

AC XY:

59947

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.947

AC:

39336

AN:

41548

American (AMR)

AF:

0.705

AC:

10778

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

2432

AN:

3470

East Asian (EAS)

AF:

0.823

AC:

4245

AN:

5160

South Asian (SAS)

AF:

0.879

AC:

4249

AN:

4832

European-Finnish (FIN)

AF:

0.790

AC:

8372

AN:

10592

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.738

AC:

50173

AN:

67966

Other (OTH)

AF:

0.772

AC:

1631

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1226

2451

3677

4902

6128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.752

Hom.:

18811

Bravo

AF:

0.798

Asia WGS

AF:

0.834

AC:

2899

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

(source)

DANN

Benign

0.34

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over