11-117203583-T-C

Position:

• chr11-117203583-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003186.5(TAGLN):​c.358+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,417,774 control chromosomes in the GnomAD database, including 13,285 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (4518 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8767 hom.)
• Consequence: TAGLN NM_003186.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.27

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAGLN	NM_003186.5	c.358+99T>C		intron_variant		ENST00000392951.9	NP_003177.2
TAGLN	NM_001001522.2	c.358+99T>C		intron_variant			NP_001001522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAGLN	ENST00000392951.9	c.358+99T>C		intron_variant		1	NM_003186.5	ENSP00000376678.4

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28983 AN: 151884 Hom.: 4511 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.102 AC: 129067 AN: 1265772 Hom.: 8767 Cov.: 18 AF XY: 0.101 AC XY: 63462 AN XY: 628714

Gnomad4 AFR exome AF: 0.452

Gnomad4 AMR exome AF: 0.0910

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0884

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.191 AC: 29009 AN: 152002 Hom.: 4518 Cov.: 32 AF XY: 0.188 AC XY: 13998 AN XY: 74322

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0949

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.173

Alfa AF: 0.126 Hom.: 458

Bravo AF: 0.205

Asia WGS AF: 0.120 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0090
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs2269397; hg19: chr11-117074299;