17-59881060-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_016261.4(TUBD1):​c.371G>A​(p.Arg124Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,996 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000054 ( 6 hom. )

Consequence

TUBD1
NM_016261.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.816
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13743839).
BP6
Variant 17-59881060-C-T is Benign according to our data. Variant chr17-59881060-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2537783.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TUBD1NM_016261.4 linkuse as main transcriptc.371G>A p.Arg124Gln missense_variant 4/9 ENST00000325752.8 NP_057345.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TUBD1ENST00000325752.8 linkuse as main transcriptc.371G>A p.Arg124Gln missense_variant 4/95 NM_016261.4 ENSP00000320797 P1Q9UJT1-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152136
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000994
AC:
25
AN:
251444
Hom.:
2
AF XY:
0.000177
AC XY:
24
AN XY:
135890
show subpopulations
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 SAS exome
AF:
0.000751
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000540
AC:
79
AN:
1461860
Hom.:
6
Cov.:
31
AF XY:
0.0000866
AC XY:
63
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000707
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152136
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.000123
AC:
15

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 18, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
14
DANN
Benign
0.67
DEOGEN2
Benign
0.073
.;T;.;.;.;T;T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.78
T;T;T;T;.;.;D
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.14
T;T;T;T;T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.0
L;L;L;L;L;L;.
MutationTaster
Benign
0.79
D;D;D;D;D;D;D
PrimateAI
Benign
0.22
T
PROVEAN
Benign
0.040
.;N;N;N;N;.;.
REVEL
Benign
0.12
Sift
Benign
1.0
.;T;T;T;T;.;.
Sift4G
Benign
0.51
T;T;T;T;T;T;.
Polyphen
0.12, 0.030
.;B;B;.;.;B;.
Vest4
0.21
MutPred
0.80
Gain of catalytic residue at R124 (P = 0.0138);Gain of catalytic residue at R124 (P = 0.0138);Gain of catalytic residue at R124 (P = 0.0138);Gain of catalytic residue at R124 (P = 0.0138);Gain of catalytic residue at R124 (P = 0.0138);Gain of catalytic residue at R124 (P = 0.0138);.;
MVP
0.64
MPC
0.13
ClinPred
0.039
T
GERP RS
3.8
Varity_R
0.061
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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.

Other links and lift over

dbSNP: rs773282613; hg19: chr17-57958421; API