rs143022570

Variant names:

• chr11-117204287-G-A
• rs143022570
• NM_003186.5:c.534G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-117204287-G-A
• chr11-117204287-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003186.5(TAGLN):​c.534G>A​(p.Gln178Gln) variant causes a synonymous change. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.53

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]

PCSK7 (HGNC:8748): (proprotein convertase subtilisin/kexin type 7) This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It can process proalbumin and is thought to be responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene has been implicated in the transcriptional regulation of housekeeping genes and plays a role in the regulation of iron metabolism. A t(11;14)(q23;q32) chromosome translocation associated with B-cell lymphoma occurs between this gene and its inverted counterpart. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAGLN	NM_003186.5	c.534G>A	p.Gln178Gln	synonymous_variant	Exon 5 of 5	ENST00000392951.9	NP_003177.2
TAGLN	NM_001001522.2	c.534G>A	p.Gln178Gln	synonymous_variant	Exon 5 of 5		NP_001001522.1
PCSK7	NM_004716.4	c.*1710C>T		downstream_gene_variant		ENST00000320934.8	NP_004707.2
PCSK7	XM_006718940.5	c.*1710C>T		downstream_gene_variant			XP_006719003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAGLN	ENST00000392951.9	c.534G>A	p.Gln178Gln	synonymous_variant	Exon 5 of 5	1	NM_003186.5	ENSP00000376678.4
PCSK7	ENST00000320934.8	c.*1710C>T		downstream_gene_variant		1	NM_004716.4	ENSP00000325917.3

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
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.2
DANN	Benign	0.90

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: rs143022570; hg19: chr11-117075003;