11-33065897-G-A

Position:

• chr11-33065897-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018393.4(TCP11L1):​c.1040G>A​(p.Gly347Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP11L1	NM_018393.4	c.1040G>A	p.Gly347Glu	missense_variant	8/10	ENST00000334274.9	NP_060863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000334274.9	c.1040G>A	p.Gly347Glu	missense_variant	8/10	1	NM_018393.4	ENSP00000335595.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 16, 2023

The c.1040G>A (p.G347E) alteration is located in exon 8 (coding exon 7) of the TCP11L1 gene. This alteration results from a G to A substitution at nucleotide position 1040, causing the glycine (G) at amino acid position 347 to be replaced by a glutamic acid (E). 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	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	.;D;.
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M;M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.87
MutPred		0.86		Loss of catalytic residue at A348 (P = 0.1496);Loss of catalytic residue at A348 (P = 0.1496);Loss of catalytic residue at A348 (P = 0.1496);
MVP		0.52
MPC		1.0
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.50
gMVP		0.73

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: chr11-33087443;