11-33043847-T-C

Variant names:

• chr11-33043847-T-C
• NM_018393.4:c.74T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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: 0.240
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100323886).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018393.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11L1	NM_018393.4	MANE Select	c.74T>C	p.Leu25Pro	missense	Exon 2 of 10	NP_060863.3
	TCP11L1	NM_001145541.1		c.74T>C	p.Leu25Pro	missense	Exon 2 of 10	NP_001139013.1	Q9NUJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11L1	ENST00000334274.9	TSL:1 MANE Select	c.74T>C	p.Leu25Pro	missense	Exon 2 of 10	ENSP00000335595.4	Q9NUJ3
	TCP11L1	ENST00000862423.1		c.74T>C	p.Leu25Pro	missense	Exon 2 of 10	ENSP00000532482.1
	TCP11L1	ENST00000432887.5	TSL:5	c.74T>C	p.Leu25Pro	missense	Exon 2 of 10	ENSP00000395070.1	Q9NUJ3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.24
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.040
Sift	Benign	0.36	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.23		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
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chr11-33065393;