Variant rs3168277 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018393.4(TCP11L1):c.1523G>A(p.Arg508Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,613,992 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0078 ( 3 hom., cov: 32)

Exomes 𝑓: 0.012 ( 138 hom. )

Consequence

TCP11L1
NM_018393.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.333

Variant links:

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]

TCP11L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040433407).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP11L1	NM_018393.4 linkuse as main transcript	c.1523G>A	p.Arg508Gln	missense_variant	10/10	ENST00000334274.9	NP_060863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000334274.9 linkuse as main transcript	c.1523G>A	p.Arg508Gln	missense_variant	10/10	1	NM_018393.4	ENSP00000335595	P1

Frequencies

GnomAD3 genomes

AF:

0.00784

AC:

1192

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.00908

AC:

2282

AN:

251424

Hom.:

AF XY:

0.00952

AC XY:

1293

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0119

AC:

17408

AN:

1461838

Hom.:

138

Cov.:

AF XY:

0.0117

AC XY:

8523

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00224

Gnomad4 FIN exome

AF:

0.0173

Gnomad4 NFE exome

AF:

0.0138

Gnomad4 OTH exome

AF:

0.00972

GnomAD4 genome

AF:

0.00782

AC:

1190

AN:

152154

Hom.:

Cov.:

AF XY:

0.00770

AC XY:

573

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00854

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00685

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0130

AC:

112

ExAC

AF:

0.00945

AC:

1148

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0120

EpiControl

AF:

0.0126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0024

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.56

.;T;.

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.27

N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.68

N;N;N

REVEL

Benign

0.013

Sift

Benign

0.26

T;T;T

Sift4G

Uncertain

0.049

D;D;D

Polyphen

0.0070

B;B;B

Vest4

0.072

MVP

0.067

MPC

0.33

ClinPred

0.0083

GERP RS

1.3

Varity_R

0.014

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over