rs2269397

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-117203583-T-A
• chr11-117203583-T-C
• chr11-117203583-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003186.5(TAGLN):​c.358+99T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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>A		intron	N/A	NP_003177.2
	TAGLN	NM_001001522.2		c.358+99T>A		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>A		intron	N/A	ENSP00000376678.4	Q01995
	TAGLN	ENST00000278968.10	TSL:1	c.358+99T>A		intron	N/A	ENSP00000278968.6	Q01995
	TAGLN	ENST00000530649.5	TSL:1	c.358+99T>A		intron	N/A	ENSP00000431941.1	Q01995

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 18

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0070
DANN	Benign	0.56
PhyloP100		-5.3
PromoterAI		-0.020	Neutral

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;