11-33043826-C-G

Variant names:

• chr11-33043826-C-G
• NM_018393.4:c.53C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018393.4(TCP11L1):​c.53C>G​(p.Ser18Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116007715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP11L1	NM_018393.4	c.53C>G	p.Ser18Cys	missense_variant	Exon 2 of 10	ENST00000334274.9	NP_060863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000334274.9	c.53C>G	p.Ser18Cys	missense_variant	Exon 2 of 10	1	NM_018393.4	ENSP00000335595.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53C>G (p.S18C) alteration is located in exon 2 (coding exon 1) of the TCP11L1 gene. This alteration results from a C to G substitution at nucleotide position 53, causing the serine (S) at amino acid position 18 to be replaced by a cysteine (C). 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	0.073
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.013	.;T;T;T;T;T
Eigen	Benign	0.043
Eigen_PC	Benign	0.021
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.71	T;.;T;T;T;.
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;M;.;M;.;M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.6	D;N;.;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.030	D;T;.;T;D;T
Sift4G	Uncertain	0.058	T;D;T;D;D;D
Polyphen		0.72	.;P;.;P;.;P
Vest4		0.27, 0.27
MutPred		0.19		Loss of phosphorylation at S18 (P = 0.0101);Loss of phosphorylation at S18 (P = 0.0101);Loss of phosphorylation at S18 (P = 0.0101);Loss of phosphorylation at S18 (P = 0.0101);Loss of phosphorylation at S18 (P = 0.0101);Loss of phosphorylation at S18 (P = 0.0101);
MVP		0.34
MPC		0.60
ClinPred		0.83	D
GERP RS		4.1
Varity_R		0.079
gMVP		0.33

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: chr11-33065372;