Variant 17-59886185-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016261.4(TUBD1):c.218T>C(p.Ile73Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000083 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

TUBD1
NM_016261.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Variant links:

Genes affected

TUBD1 (HGNC:16811): (tubulin delta 1) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization; mitotic cell cycle; and positive regulation of smoothened signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TUBD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBD1	NM_016261.4 linkuse as main transcript	c.218T>C	p.Ile73Thr	missense_variant	3/9	ENST00000325752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBD1	ENST00000325752.8 linkuse as main transcript	c.218T>C	p.Ile73Thr	missense_variant	3/9	5	NM_016261.4	P1	Q9UJT1-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251340

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000869

AC:

127

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000354

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2024

The c.218T>C (p.I73T) alteration is located in exon 3 (coding exon 2) of the TUBD1 gene. This alteration results from a T to C substitution at nucleotide position 218, causing the isoleucine (I) at amino acid position 73 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

.;T;.;.;.;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

T;T;T;T;.;.;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.96

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.14

MutationAssessor

Pathogenic

2.9

M;M;M;M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-4.3

.;D;D;D;D;.;.

REVEL

Pathogenic

0.70

Sift

Uncertain

0.016

.;D;D;D;D;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;.

Polyphen

0.24, 0.21

.;B;B;.;.;B;.

Vest4

0.39

MutPred

0.90

Gain of disorder (P = 0.0296);Gain of disorder (P = 0.0296);Gain of disorder (P = 0.0296);Gain of disorder (P = 0.0296);Gain of disorder (P = 0.0296);Gain of disorder (P = 0.0296);.;

MVP

0.85

MPC

0.28

ClinPred

0.43

GERP RS

6.1

Varity_R

0.63

gMVP

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over