chr16-1223982-C-T

Position:

• chr16-1223982-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012467.4(TPSG1):​c.74-388G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 227,830 control chromosomes in the GnomAD database, including 22,649 homozygotes. 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: 𝑓 0.45 (15386 hom., cov: 27)
  • Exomes 𝑓: 0.39 (7263 hom.)
• Consequence: TPSG1 NM_012467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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]

ENSG00000277010 (HGNC:1395): (calcium voltage-gated channel subunit alpha1 H) This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). [provided by RefSeq, Jul 2008]

TPSG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPSG1	NM_012467.4	c.74-388G>A		intron_variant		ENST00000234798.5	NP_036599.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPSG1	ENST00000234798.5	c.74-388G>A		intron_variant		1	NM_012467.4	ENSP00000234798.4
ENSG00000277010	ENST00000621827.1	n.344C>T		non_coding_transcript_exon_variant	1/1	6		ENSP00000518766.1
TPSG1	ENST00000564684.1	n.175-388G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.448 AC: 66847 AN: 149186 Hom.: 15398 Cov.: 27

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.391 AC: 30676 AN: 78534 Hom.: 7263 Cov.: 0 AF XY: 0.386 AC XY: 15404 AN XY: 39864

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.742

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.448 AC: 66859 AN: 149296 Hom.: 15386 Cov.: 27 AF XY: 0.454 AC XY: 33052 AN XY: 72780

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.453

Alfa AF: 0.427 Hom.: 2510

Bravo AF: 0.432

Asia WGS AF: 0.516 AC: 1791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.98
DANN	Benign	0.69

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: rs12934797; hg19: chr16-1273982;