chr11-33061646-A-G

Variant names:

• chr11-33061646-A-G
• NM_018393.4:c.892A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018393.4(TCP11L1):​c.892A>G​(p.Arg298Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.804

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051106334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP11L1	NM_018393.4	c.892A>G	p.Arg298Gly	missense_variant	Exon 7 of 10	ENST00000334274.9	NP_060863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000334274.9	c.892A>G	p.Arg298Gly	missense_variant	Exon 7 of 10	1	NM_018393.4	ENSP00000335595.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.892A>G (p.R298G) alteration is located in exon 7 (coding exon 6) of the TCP11L1 gene. This alteration results from a A to G substitution at nucleotide position 892, causing the arginine (R) at amino acid position 298 to be replaced by a glycine (G). 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	0.053
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.22
DANN	Benign	0.71
DEOGEN2	Benign	0.0029	T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.43	.;T;.
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.051	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.15	N;N;N
REVEL	Benign	0.028
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.099
MutPred		0.38		Loss of solvent accessibility (P = 0.0329);Loss of solvent accessibility (P = 0.0329);Loss of solvent accessibility (P = 0.0329);
MVP		0.030
MPC		0.33
ClinPred		0.063	T
GERP RS		-11
Varity_R		0.044
gMVP		0.091

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: chr11-33083192;