rs377129017

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-33057213-A-C
• chr11-33057213-A-G
• chr11-33057213-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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 Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP11L1	NM_018393.4	c.395A>C	p.Lys132Thr	missense_variant	Exon 4 of 10	ENST00000334274.9	NP_060863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000334274.9	c.395A>C	p.Lys132Thr	missense_variant	Exon 4 of 10	1	NM_018393.4	ENSP00000335595.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.0092
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D;.;D;.
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	.;M;M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	D;D;D;D
REVEL	Benign	0.083
Sift	Benign	0.069	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.80	.;P;P;P
Vest4		0.30, 0.30
MutPred		0.51		Loss of methylation at K132 (P = 0.0108);Loss of methylation at K132 (P = 0.0108);Loss of methylation at K132 (P = 0.0108);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

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: chr11-33078759;