6-167340442-C-T

Variant summary

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

The NM_031949.5(TTLL2):​c.542C>T​(p.Thr181Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,614,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

TTLL2
NM_031949.5 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14
Variant links:
Genes affected
TTLL2 (HGNC:21211): (tubulin tyrosine ligase like 2) Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization and protein polyglutamylation. Predicted to be active in cilium. [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 rank MANE Protein UniProt
TTLL2NM_031949.5 linkc.542C>T p.Thr181Met missense_variant Exon 3 of 3 ENST00000239587.10 NP_114155.4 Q9BWV7
TTLL2NM_001410948.1 linkc.323C>T p.Thr108Met missense_variant Exon 2 of 2 NP_001397877.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTLL2ENST00000239587.10 linkc.542C>T p.Thr181Met missense_variant Exon 3 of 3 1 NM_031949.5 ENSP00000239587.5 Q9BWV7
TTLL2ENST00000515138.1 linkn.542C>T non_coding_transcript_exon_variant Exon 3 of 6 1 ENSP00000424130.1 Q9BWV7
TTLL2ENST00000649884.1 linkc.323C>T p.Thr108Met missense_variant Exon 2 of 2 ENSP00000497040.1 A0A3B3IRU1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152170
Hom.:
0
Cov.:
32
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:
0.000192
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:
0.0000557
AC:
14
AN:
251462
Hom.:
0
AF XY:
0.0000809
AC XY:
11
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000105
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000903
AC:
132
AN:
1461890
Hom.:
0
Cov.:
36
AF XY:
0.0000935
AC XY:
68
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000111
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000969
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.000296

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.542C>T (p.T181M) alteration is located in exon 3 (coding exon 3) of the TTLL2 gene. This alteration results from a C to T substitution at nucleotide position 542, causing the threonine (T) at amino acid position 181 to be replaced by a methionine (M). 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
0.25
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
.;T
Eigen
Benign
0.17
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.80
T;.
M_CAP
Benign
0.0012
T
MetaRNN
Uncertain
0.50
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
4.4
.;H
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-3.7
.;D
REVEL
Benign
0.21
Sift
Uncertain
0.0050
.;D
Sift4G
Uncertain
0.015
.;D
Polyphen
1.0
.;D
Vest4
0.46
MVP
0.048
MPC
0.53
ClinPred
1.0
D
GERP RS
2.6
Varity_R
0.56
gMVP
0.70

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: rs199812982; hg19: chr6-167753930; API