11-117203583-T-C

Variant names:

• chr11-117203583-T-C
• rs2269397
• NM_003186.5:c.358+99T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003186.5. 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
	TAGLN	NM_003186.5	MANE Select	c.358+99T>C		intron	N/A	NP_003177.2
	TAGLN	NM_001001522.2		c.358+99T>C		intron	N/A	NP_001001522.1	Q01995

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAGLN	ENST00000392951.9	TSL:1 MANE Select	c.358+99T>C		intron	N/A	ENSP00000376678.4	Q01995
	TAGLN	ENST00000278968.10	TSL:1	c.358+99T>C		intron	N/A	ENSP00000278968.6	Q01995
	TAGLN	ENST00000530649.5	TSL:1	c.358+99T>C		intron	N/A	ENSP00000431941.1	Q01995

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

African (AFR) AF: 0.452 AC: 13489 AN: 29840

American (AMR) AF: 0.0910 AC: 3425 AN: 37658

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3078 AN: 22424

East Asian (EAS) AF: 0.108 AC: 4032 AN: 37456

South Asian (SAS) AF: 0.107 AC: 7947 AN: 74296

European-Finnish (FIN) AF: 0.107 AC: 4761 AN: 44624

Middle Eastern (MID) AF: 0.169 AC: 699 AN: 4124

European-Non Finnish (NFE) AF: 0.0884 AC: 85051 AN: 961828

Other (OTH) AF: 0.123 AC: 6585 AN: 53522

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

African (AFR) AF: 0.435 AC: 17998 AN: 41388

American (AMR) AF: 0.117 AC: 1793 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3470

East Asian (EAS) AF: 0.0949 AC: 490 AN: 5164

South Asian (SAS) AF: 0.113 AC: 547 AN: 4820

European-Finnish (FIN) AF: 0.104 AC: 1103 AN: 10590

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.0906 AC: 6156 AN: 67962

Other (OTH) AF: 0.173 AC: 366 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0090
DANN	Benign	0.36
PhyloP100		-5.3
PromoterAI		-0.0083	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2269397; hg19: chr11-117074299;