rs58623186

Variant names:

• chr16-1221970-C-G
• rs58623186
• NM_012467.4:c.784G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-1221970-C-G
• chr16-1221970-C-T

Variant summary

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

The NM_012467.4(TPSG1):​c.784G>C​(p.Val262Leu) variant causes a missense 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. 14/19 in silico tools predict 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: 34)
• Consequence: TPSG1 NM_012467.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90

Genes affected

TPSG1 (HGNC:14134): (tryptase gamma 1) Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. There is uncertainty regarding the number of genes in this cluster. Currently four functional genes - alpha I, beta I, beta II and gamma I - have been identified. And beta I has an allelic variant named alpha II, beta II has an allelic variant beta III, also gamma I has an allelic variant gamma II. Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha-tryptases predominant. This gene differs from other members of the tryptase gene family in that it has C-terminal hydrophobic domain, which may serve as a membrane anchor. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. [provided by RefSeq, Jul 2008]

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 (MetaRNN=0.14899623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPSG1	NM_012467.4	c.784G>C	p.Val262Leu	missense_variant	Exon 6 of 6	ENST00000234798.5	NP_036599.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPSG1	ENST00000234798.5	c.784G>C	p.Val262Leu	missense_variant	Exon 6 of 6	1	NM_012467.4	ENSP00000234798.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 77

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.12
DANN	Benign	0.42
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0054	N
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.36	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.29
Sift	Benign	0.48	T
Sift4G	Benign	0.75	T
Vest4		0.074
MutPred		0.53		Loss of MoRF binding (P = 0.1092);
MVP		0.53
MPC		0.0076
ClinPred		0.18	T
GERP RS		0.65
gMVP		0.37

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: rs58623186; hg19: chr16-1271970;