rs2824814

chr21-18416800-T-Cchr21-18416800-T-A

Variant summary

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

The ENST00000422787.1(TMPRSS15):c.11-18471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,790 control chromosomes in the GnomAD database, including 31,369 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 0.64 (31369 hom., cov: 32)
• Consequence: TMPRSS15 ENST00000422787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

Genes affected

TMPRSS15 (HGNC:9490): (transmembrane serine protease 15) This gene encodes an enzyme that converts the pancreatic proenzyme trypsinogen to trypsin, which activates other proenzymes including chymotrypsinogen and procarboxypeptidases. The precursor protein is cleaved into two chains that form a heterodimer linked by a disulfide bond. This protein is a member of the trypsin family of peptidases. Mutations in this gene cause enterokinase deficiency, a malabsorption disorder characterized by diarrhea and failure to thrive. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS15	XM_047440912.1	c.-172-10594A>G		intron_variant
TMPRSS15	XM_047440913.1	c.-172-10594A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS15	ENST00000422787.1	c.11-18471A>G		intron_variant		5
TMPRSS15	ENST00000474775.1	c.-277-33022A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96839 AN: 151672 Hom.: 31355 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.638 AC: 96881 AN: 151790 Hom.: 31369 Cov.: 32 AF XY: 0.638 AC XY: 47317 AN XY: 74186

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.655

Alfa AF: 0.674 Hom.: 17162

Bravo AF: 0.641

Asia WGS AF: 0.540 AC: 1873 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.1
Dann	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2824814; hg19: chr21-19789117;