11-117203191-G-T

Variant names:

• chr11-117203191-G-T
• rs149213147
• NM_003186.5:c.178G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003186.5(TAGLN):​c.178G>T​(p.Val60Leu) variant causes a missense, splice region 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. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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 missense, splice_region
• Scores: Splicing: ADA: 0.8822
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39468664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAGLN	NM_003186.5	c.178G>T	p.Val60Leu	missense_variant, splice_region_variant	Exon 2 of 5	ENST00000392951.9	NP_003177.2
TAGLN	NM_001001522.2	c.178G>T	p.Val60Leu	missense_variant, splice_region_variant	Exon 2 of 5		NP_001001522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAGLN	ENST00000392951.9	c.178G>T	p.Val60Leu	missense_variant, splice_region_variant	Exon 2 of 5	1	NM_003186.5	ENSP00000376678.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.77	D;D;D;.;D;D
Eigen	Benign	-0.054
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.90	.;.;.;D;.;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.39	T;T;T;T;T;T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.4	L;L;L;.;L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.10	T;T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;B;B
Vest4		0.15
MutPred		0.53		Loss of MoRF binding (P = 0.0932);Loss of MoRF binding (P = 0.0932);Loss of MoRF binding (P = 0.0932);Loss of MoRF binding (P = 0.0932);Loss of MoRF binding (P = 0.0932);Loss of MoRF binding (P = 0.0932);
MVP		0.92
MPC		0.17
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.11
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.88
dbscSNV1_RF	Pathogenic	0.73
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: rs149213147; hg19: chr11-117073907;