11-117203583-T-G

Variant names:

• chr11-117203583-T-G
• rs2269397
• NM_003186.5:c.358+99T>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>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,266,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000016 (0 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: 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAGLN	NM_003186.5	MANE Select	c.358+99T>G		intron	N/A	NP_003177.2
	TAGLN	NM_001001522.2		c.358+99T>G		intron	N/A	NP_001001522.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1266672 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 629168

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29886

American (AMR) AF: 0.00 AC: 0 AN: 37672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22432

East Asian (EAS) AF: 0.00 AC: 0 AN: 37464

South Asian (SAS) AF: 0.00 AC: 0 AN: 74328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 962544

Other (OTH) AF: 0.0000187 AC: 1 AN: 53560

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.0080
DANN	Benign	0.44
PhyloP100		-5.3
PromoterAI		-0.012	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;