dbSNP rs2451214: TBCD:c.235+963T>C (chr17-82757178-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_005993.5(TBCD):c.235+963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,058 control chromosomes in the GnomAD database, including 29,556 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 0.62 ( 29556 hom., cov: 32)

Consequence

TBCD
NM_005993.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.69

Publications

13 publications found

Variant links:

Genes affected

TBCD (HGNC:11581): (tubulin folding cofactor D) Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]

TBCD Gene-Disease associations (from GenCC):

early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

TBCD links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005993.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005993.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBCD	NM_005993.5	MANE Select	c.235+963T>C	intron	N/A	NP_005984.3
TBCD	NM_001411101.1		c.184+4801T>C	intron	N/A	NP_001398030.1	A0A804HLI2
TBCD	NM_001411102.1		c.235+963T>C	intron	N/A	NP_001398031.1	A0A804HJ32

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBCD	ENST00000355528.9	TSL:1 MANE Select	c.235+963T>C	intron	N/A	ENSP00000347719.4	Q9BTW9-1
TBCD	ENST00000684760.1		c.235+963T>C	intron	N/A	ENSP00000507696.1	A0A804HJY5
TBCD	ENST00000684349.1		c.235+963T>C	intron	N/A	ENSP00000508067.1	A0A804HKT8

Frequencies

GnomAD3 genomes

AF:

0.622

AC:

94573

AN:

151938

Hom.:

29499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.654

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.591

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.604

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.608

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.613

Gnomad OTH

AF:

0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.623

AC:

94691

AN:

152058

Hom.:

29556

Cov.:

AF XY:

0.623

AC XY:

46333

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.654

AC:

27134

AN:

41476

American (AMR)

AF:

0.592

AC:

9042

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2170

AN:

3466

East Asian (EAS)

AF:

0.604

AC:

3118

AN:

5166

South Asian (SAS)

AF:

0.641

AC:

3090

AN:

4818

European-Finnish (FIN)

AF:

0.608

AC:

6422

AN:

10564

Middle Eastern (MID)

AF:

0.582

AC:

170

AN:

292

European-Non Finnish (NFE)

AF:

0.613

AC:

41638

AN:

67974

Other (OTH)

AF:

0.625

AC:

1320

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1862

3724

5586

7448

9310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.629

Hom.:

5941

Bravo

AF:

0.620

Asia WGS

AF:

0.638

AC:

2219

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.48

(source)

DANN

Benign

0.69

PhyloP100

-3.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over