chr11-33057213-A-C

Variant names:

• chr11-33057213-A-C
• rs377129017
• NM_018393.4:c.395A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018393.4(TCP11L1):​c.395A>C​(p.Lys132Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K132R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37350062).

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.395A>C	p.Lys132Thr	missense	Exon 4 of 10	NP_060863.3
	TCP11L1	NM_001145541.1		c.395A>C	p.Lys132Thr	missense	Exon 4 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.395A>C	p.Lys132Thr	missense	Exon 4 of 10	ENSP00000335595.4	Q9NUJ3
	TCP11L1	ENST00000862423.1		c.395A>C	p.Lys132Thr	missense	Exon 4 of 10	ENSP00000532482.1
	TCP11L1	ENST00000432887.5	TSL:5	c.395A>C	p.Lys132Thr	missense	Exon 4 of 10	ENSP00000395070.1	Q9NUJ3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.0092
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.083
Sift	Benign	0.069	T
Sift4G	Benign	0.20	T
Polyphen		0.80	P
Vest4		0.30
MutPred		0.51		Loss of methylation at K132 (P = 0.0108)
MVP		0.29
MPC		0.42
ClinPred		0.95	D
GERP RS		2.1
Varity_R		0.12
gMVP		0.43
Mutation Taster		=71/29	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

dbSNP: rs377129017; hg19: chr11-33078759;