11-33058069-C-G

Variant summary

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

The NM_018393.4(TCP11L1):​c.568C>G​(p.Leu190Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TCP11L1
NM_018393.4 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
Variant links:
Genes affected
TCP11L1 (HGNC:25655): (t-complex 11 like 1) Predicted to be involved in signal transduction. Located in microtubule. [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
TCP11L1NM_018393.4 linkc.568C>G p.Leu190Val missense_variant Exon 5 of 10 ENST00000334274.9 NP_060863.3 Q9NUJ3B3KQZ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCP11L1ENST00000334274.9 linkc.568C>G p.Leu190Val missense_variant Exon 5 of 10 1 NM_018393.4 ENSP00000335595.4 Q9NUJ3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.568C>G (p.L190V) alteration is located in exon 5 (coding exon 4) of the TCP11L1 gene. This alteration results from a C to G substitution at nucleotide position 568, causing the leucine (L) at amino acid position 190 to be replaced by a valine (V). 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
0.22
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;T;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.86
.;D;.
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.50
D;D;D
MetaSVM
Benign
-0.90
T
MutationAssessor
Pathogenic
3.5
H;H;H
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.7
D;D;D
REVEL
Benign
0.24
Sift
Uncertain
0.0050
D;D;D
Sift4G
Uncertain
0.017
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.36
MutPred
0.72
Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP
0.29
MPC
0.42
ClinPred
0.93
D
GERP RS
4.6
Varity_R
0.25
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-33079615; API