11-33043847-T-C

Position:

• chr11-33043847-T-C

Variant summary

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

The NM_018393.4(TCP11L1):​c.74T>C​(p.Leu25Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.240

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]

TCP11L1 (HGNC:):

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=0.100323886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP11L1	NM_018393.4	c.74T>C	p.Leu25Pro	missense_variant	2/10	ENST00000334274.9	NP_060863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000334274.9	c.74T>C	p.Leu25Pro	missense_variant	2/10	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 16, 2024

The c.74T>C (p.L25P) alteration is located in exon 2 (coding exon 1) of the TCP11L1 gene. This alteration results from a T to C substitution at nucleotide position 74, causing the leucine (L) at amino acid position 25 to be replaced by a proline (P). 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	0.070
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.0054	.;T;T;T;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.46	T;.;T;T;T;.
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.10	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.;L;.;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.50	N;N;.;N;D;N
REVEL	Benign	0.040
Sift	Benign	0.36	T;T;.;T;D;T
Sift4G	Benign	0.34	T;T;T;T;D;T
Polyphen		0.0	.;B;.;B;.;B
Vest4		0.13, 0.13
MutPred		0.23		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP		0.20
MPC		0.41
ClinPred		0.037	T
GERP RS		0.46
Varity_R		0.048
gMVP		0.26

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: chr11-33065393;