Genetic Variant TUBGCP6:p.Thr1100Thr (chr22-50221059-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_020461.4(TUBGCP6):c.3300T>C(p.Thr1100Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBGCP6
NM_020461.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 22-50221059-A-G is Benign according to our data. Variant chr22-50221059-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 437150.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TUBGCP6	NM_020461.4 link	c.3300T>C	p.Thr1100Thr	synonymous_variant	Exon 16 of 25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3 link	n.3864T>C		non_coding_transcript_exon_variant	Exon 16 of 20
TUBGCP6	XR_938347.3 link	n.3864T>C		non_coding_transcript_exon_variant	Exon 16 of 23
TUBGCP6	XR_007067982.1 link	n.3048+969T>C		intron_variant	Intron 15 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TUBGCP6	ENST00000248846.10 link	c.3300T>C	p.Thr1100Thr	synonymous_variant	Exon 16 of 25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.7 link	n.3300T>C		non_coding_transcript_exon_variant	Exon 16 of 25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5 link	n.3617+216T>C		intron_variant	Intron 16 of 22	1
TUBGCP6	ENST00000491449.5 link	n.1607T>C		non_coding_transcript_exon_variant	Exon 8 of 16	5

Frequencies

GnomAD3 genomes

AF:

0.000971

AC:

AN:

91700

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00144

Gnomad AMI

AF:

0.00218

Gnomad AMR

AF:

0.000933

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00185

Gnomad FIN

AF:

0.000380

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000709

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

247326

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.07e-7

AC:

AN:

1414462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704286

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31478

American (AMR)

AF:

0.0000237

AC:

AN:

42218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23712

East Asian (EAS)

AF:

0.00

AC:

AN:

37154

South Asian (SAS)

AF:

0.00

AC:

AN:

85248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5492

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080568

Other (OTH)

AF:

0.00

AC:

AN:

56614

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000980

AC:

AN:

91794

Hom.:

Cov.:

AF XY:

0.000744

AC XY:

AN XY:

44342

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00147

AC:

AN:

23062

American (AMR)

AF:

0.000931

AC:

AN:

8594

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

2314

East Asian (EAS)

AF:

0.00135

AC:

AN:

2968

South Asian (SAS)

AF:

0.00185

AC:

AN:

2702

European-Finnish (FIN)

AF:

0.000380

AC:

AN:

5268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000709

AC:

AN:

45108

Other (OTH)

AF:

0.00

AC:

AN:

1226

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.257

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0862

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 01, 2017

Genetic Services Laboratory, University of Chicago

Significance:Likely 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

-0.86

CADD

Benign

0.90

(source)

DANN

Benign

0.40

PhyloP100

-1.7

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over