chr11-117203191-G-A

Position:

chr11-117203191-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003186.5(TAGLN):c.178G>A(p.Val60Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,589,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TAGLN
NM_003186.5 missense, splice_region

Scores

Splicing: ADA: 0.9884

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

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:

TAGLN (HGNC:):

TAGLN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAGLN	NM_003186.5 linkuse as main transcript	c.178G>A	p.Val60Met	missense_variant, splice_region_variant	2/5	ENST00000392951.9	NP_003177.2	Q01995Q5U0D2
TAGLN	NM_001001522.2 linkuse as main transcript	c.178G>A	p.Val60Met	missense_variant, splice_region_variant	2/5		NP_001001522.1	Q01995Q5U0D2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAGLN	ENST00000392951.9 linkuse as main transcript	c.178G>A	p.Val60Met	missense_variant, splice_region_variant	2/5	1	NM_003186.5	ENSP00000376678.4		Q01995

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000764

AC:

AN:

235484

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

126616

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000195

AC:

280

AN:

1436986

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

152

AN XY:

711070

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.0000698

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000241

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000225

Gnomad4 OTH exome

AF:

0.000439

GnomAD4 genome

AF:

0.000144

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.178G>A (p.V60M) alteration is located in exon 2 (coding exon 1) of the TAGLN gene. This alteration results from a G to A substitution at nucleotide position 178, causing the valine (V) at amino acid position 60 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

D;D;D;.;D;D

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.90

.;.;.;D;.;D

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.33

T;T;T;T;T;T

MetaSVM

Pathogenic

0.86

MutationAssessor

Uncertain

2.2

M;M;M;.;M;M

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Uncertain

0.52

Sift

Uncertain

0.019

D;D;D;D;D;D

Sift4G

Uncertain

0.034

D;D;D;T;D;D

Polyphen

0.89

P;P;P;.;P;P

Vest4

0.19

MVP

0.96

MPC

0.21

ClinPred

0.070

GERP RS

4.7

Varity_R

0.077

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.86

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over