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

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.1523G>A	p.Arg508Gln	missense	Exon 10 of 10	NP_060863.3
	TCP11L1	NM_001145541.1		c.1523G>A	p.Arg508Gln	missense	Exon 10 of 10	NP_001139013.1	Q9NUJ3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCP11L1	ENST00000334274.9	TSL:1 MANE Select	c.1523G>A	p.Arg508Gln	missense	Exon 10 of 10	ENSP00000335595.4	Q9NUJ3
TCP11L1	ENST00000862423.1		c.1538G>A	p.Arg513Gln	missense	Exon 10 of 10	ENSP00000532482.1
TCP11L1	ENST00000432887.5	TSL:5	c.1523G>A	p.Arg508Gln	missense	Exon 10 of 10	ENSP00000395070.1	Q9NUJ3

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 v4.9

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.27

PhyloP100

-0.33

PrimateAI

Benign

0.27

PROVEAN

Benign

0.68

REVEL

Benign

0.013

Sift

Benign

0.26

Sift4G

Uncertain

0.049

Polyphen

0.0070

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over