16-1256824-G-T

Variant names:

• chr16-1256824-G-T
• NM_012217.3:c.282G>T

Variant summary

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

The NM_012217.3(TPSD1):​c.282G>T​(p.Arg94Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,964 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 38)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TPSD1 NM_012217.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

Genes affected

TPSD1 (HGNC:14118): (tryptase delta 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. These genes are characterized by several distinct features. They have a highly conserved 3' UTR and contain tandem repeat sequences at the 5' flank and 3' UTR which are thought to play a role in regulation of the mRNA stability. Although this gene may be an exception, most of the tryptase genes have an intron immediately upstream of the initiator Met codon, which separates the site of transcription initiation from protein coding sequence. This feature is characteristic of tryptases but is unusual in other genes. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. This gene was once considered to be a pseudogene, although it is now believed to be a functional gene that encodes a protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPSD1	NM_012217.3	c.282G>T	p.Arg94Ser	missense_variant	Exon 3 of 5	ENST00000211076.5	NP_036349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPSD1	ENST00000211076.5	c.282G>T	p.Arg94Ser	missense_variant	Exon 3 of 5	1	NM_012217.3	ENSP00000211076.3
TPSD1	ENST00000397534.6	c.261G>T	p.Arg87Ser	missense_variant	Exon 4 of 6	5		ENSP00000380668.2

Frequencies

GnomAD3 genomes Cov.: 38

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459964 Hom.: 0 Cov.: 162 AF XY: 0.00000138 AC XY: 1 AN XY: 726308

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	-0.23	.;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.049	D;D
Polyphen		0.99	.;D
Vest4		0.51
MutPred		0.71		.;Loss of methylation at R94 (P = 0.0514);
MVP		0.70
MPC		0.053
ClinPred		0.82	D
GERP RS		1.7
Varity_R		0.61
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1306825;