rs377129017

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018393.4(TCP11L1):​c.395A>G​(p.Lys132Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,614,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000084 (0 hom.)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19930243).

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>G	p.Lys132Arg	missense	Exon 4 of 10	NP_060863.3
	TCP11L1	NM_001145541.1		c.395A>G	p.Lys132Arg	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>G	p.Lys132Arg	missense	Exon 4 of 10	ENSP00000335595.4	Q9NUJ3
	TCP11L1	ENST00000862423.1		c.395A>G	p.Lys132Arg	missense	Exon 4 of 10	ENSP00000532482.1
	TCP11L1	ENST00000432887.5	TSL:5	c.395A>G	p.Lys132Arg	missense	Exon 4 of 10	ENSP00000395070.1	Q9NUJ3

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000875 AC: 22 AN: 251430 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000841 AC: 123 AN: 1461854 Hom.: 0 Cov.: 33 AF XY: 0.000106 AC XY: 77 AN XY: 727228

African (AFR) AF: 0.000179 AC: 6 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: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86258

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

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000782 AC: 87 AN: 1111992

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

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152274 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74456

African (AFR) AF: 0.000120 AC: 5 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000945

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

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	0.073
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0078	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.085
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.12
MVP		0.19
MPC		0.23
ClinPred		0.20	T
GERP RS		2.1
Varity_R		0.046
gMVP		0.23
Mutation Taster		=94/6	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; COSMIC: COSV57516052; COSMIC: COSV57516052;