17-59878268-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016261.4(TUBD1):​c.604C>T​(p.Leu202Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TUBD1
NM_016261.4 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TUBD1NM_016261.4 linkuse as main transcriptc.604C>T p.Leu202Phe missense_variant 5/9 ENST00000325752.8 NP_057345.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TUBD1ENST00000325752.8 linkuse as main transcriptc.604C>T p.Leu202Phe missense_variant 5/95 NM_016261.4 ENSP00000320797 P1Q9UJT1-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152070
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251474
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152188
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
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 submitterclinical testingAmbry GeneticsOct 11, 2021The c.604C>T (p.L202F) alteration is located in exon 5 (coding exon 4) of the TUBD1 gene. This alteration results from a C to T substitution at nucleotide position 604, causing the leucine (L) at amino acid position 202 to be replaced by a phenylalanine (F). 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
Benign
0.15
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
.;T;.;.;.;T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.94
D;D;D;D;.;.
M_CAP
Benign
0.066
D
MetaRNN
Uncertain
0.74
D;D;D;D;D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
1.0
L;L;L;L;L;L
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-2.4
.;N;N;N;N;.
REVEL
Uncertain
0.37
Sift
Benign
0.10
.;T;D;D;D;.
Sift4G
Benign
0.13
T;T;T;T;T;T
Polyphen
0.080, 0.48
.;B;P;.;.;B
Vest4
0.63
MutPred
0.69
Loss of stability (P = 0.1243);Loss of stability (P = 0.1243);Loss of stability (P = 0.1243);Loss of stability (P = 0.1243);Loss of stability (P = 0.1243);Loss of stability (P = 0.1243);
MVP
0.83
MPC
0.39
ClinPred
0.93
D
GERP RS
5.5
Varity_R
0.36
gMVP
0.69

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.

Other links and lift over

dbSNP: rs868415094; hg19: chr17-57955629; API