chr11-117203355-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003186.5(TAGLN):c.229G>C(p.Val77Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00147 in 1,614,176 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00085 ( 19 hom. )

Consequence

TAGLN
NM_003186.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.86

Publications

4 publications found

Variant links:

Genes affected

TAGLN (HGNC:11553): (transgelin) This gene encodes a shape change and transformation sensitive actin-binding protein which belongs to the calponin family. It is ubiquitously expressed in vascular and visceral smooth muscle, and is an early marker of smooth muscle differentiation. The encoded protein is thought to be involved in calcium-independent smooth muscle contraction. It acts as a tumor suppressor, and the loss of its expression is an early event in cell transformation and the development of some tumors, coinciding with cellular plasticity. The encoded protein has a domain architecture consisting of an N-terminal calponin homology (CH) domain and a C-terminal calponin-like (CLIK) domain. Mice with a knockout of the orthologous gene are viable and fertile but their vascular smooth muscle cells exhibit alterations in the distribution of the actin filament and changes in cytoskeletal organization. [provided by RefSeq, Aug 2017]

TAGLN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010215431).

BP6

Variant 11-117203355-G-C is Benign according to our data. Variant chr11-117203355-G-C is described in ClinVar as [Benign]. Clinvar id is 791178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00743 (1132/152286) while in subpopulation AFR AF = 0.0259 (1078/41566). AF 95% confidence interval is 0.0246. There are 8 homozygotes in GnomAd4. There are 526 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1132 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAGLN	NM_003186.5 link	c.229G>C	p.Val77Leu	missense_variant	Exon 3 of 5	ENST00000392951.9	NP_003177.2	Q01995Q5U0D2
TAGLN	NM_001001522.2 link	c.229G>C	p.Val77Leu	missense_variant	Exon 3 of 5		NP_001001522.1	Q01995Q5U0D2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAGLN	ENST00000392951.9 link	c.229G>C	p.Val77Leu	missense_variant	Exon 3 of 5	1	NM_003186.5	ENSP00000376678.4		Q01995

Frequencies

GnomAD3 genomes

AF:

0.00743

AC:

1130

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00196

AC:

492

AN:

251488

AF XY:

0.00148

show subpopulations

Gnomad AFR exome

AF:

0.0263

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000852

AC:

1246

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000744

AC XY:

541

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0290

AC:

972

AN:

33480

American (AMR)

AF:

0.00163

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000486

AC:

AN:

1112010

Other (OTH)

AF:

0.00217

AC:

131

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

156

233

311

389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00743

AC:

1132

AN:

152286

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

526

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0259

AC:

1078

AN:

41566

American (AMR)

AF:

0.00229

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68016

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

115

173

230

288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.00825

ESP6500AA

AF:

0.0239

AC:

105

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00245

AC:

297

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 11, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

D;D;D;.;D;D

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

.;.;.;D;.;D

MetaRNN

Benign

0.010

T;T;T;T;T;T

MetaSVM

Uncertain

0.46

MutationAssessor

Uncertain

2.1

M;M;M;.;M;M

PhyloP100

3.9

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Uncertain

0.57

Sift

Uncertain

0.026

D;D;D;D;D;D

Sift4G

Uncertain

0.029

D;D;D;D;D;D

Polyphen

0.010

B;B;B;.;B;B

Vest4

0.45

MutPred

0.44

Loss of methylation at K78 (P = 0.0631);Loss of methylation at K78 (P = 0.0631);Loss of methylation at K78 (P = 0.0631);Loss of methylation at K78 (P = 0.0631);Loss of methylation at K78 (P = 0.0631);Loss of methylation at K78 (P = 0.0631);

MVP

0.97

MPC

0.21

ClinPred

0.019

GERP RS

4.8

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.38

gMVP

0.38

Mutation Taster

=99/1

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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chr11-117203355-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over