rs2225408

Positions:

• chr21-18415699-G-T
• chr21-18415699-G-A
• chr21-18415699-G-C

Variant summary

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

The ENST00000422787.1(TMPRSS15):​c.11-17370C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,826 control chromosomes in the GnomAD database, including 32,298 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 0.65 (32298 hom., cov: 32)
• Consequence: TMPRSS15 ENST00000422787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-1.07).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS15	XM_047440912.1	c.-172-9493C>A		intron_variant			XP_047296868.1
TMPRSS15	XM_047440913.1	c.-172-9493C>A		intron_variant			XP_047296869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS15	ENST00000422787.1	c.11-17370C>A		intron_variant		5		ENSP00000398253
TMPRSS15	ENST00000474775.1	c.-277-31921C>A		intron_variant		5		ENSP00000474811

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98542 AN: 151708 Hom.: 32271 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.649 AC: 98604 AN: 151826 Hom.: 32298 Cov.: 32 AF XY: 0.649 AC XY: 48164 AN XY: 74176

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.666

Alfa AF: 0.670 Hom.: 4296

Bravo AF: 0.653

Asia WGS AF: 0.540 AC: 1875 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.39
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2225408; hg19: chr21-19788016;