dbSNP rs3168277: TCP11L1:p.Arg508Gln (chr11-33072669-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TCP11L1	NM_018393.4 link	c.1523G>A	p.Arg508Gln	missense_variant	Exon 10 of 10	ENST00000334274.9	NP_060863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000334274.9 link	c.1523G>A	p.Arg508Gln	missense_variant	Exon 10 of 10	1	NM_018393.4	ENSP00000335595.4

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

GnomAD2 exomes

AF:

0.00908

AC:

2282

AN:

251424

AF XY:

0.00952

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 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

African (AFR)

AF:

0.00143

AC:

AN:

33480

American (AMR)

AF:

0.00371

AC:

166

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00306

AC:

AN:

26134

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.00224

AC:

193

AN:

86248

European-Finnish (FIN)

AF:

0.0173

AC:

922

AN:

53416

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0138

AC:

15393

AN:

1111980

Other (OTH)

AF:

0.00972

AC:

587

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

896

1792

2687

3583

4479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00782

AC:

1190

AN:

152154

Hom.:

Cov.:

AF XY:

0.00770

AC XY:

573

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00217

AC:

AN:

41526

American (AMR)

AF:

0.00412

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00249

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0151

AC:

160

AN:

10568

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0124

AC:

841

AN:

67996

Other (OTH)

AF:

0.00854

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0113

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

(source)

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

PhyloP100

-0.33

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

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over