rs2824791

Positions:

• chr21-18385363-G-A

Variant summary

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

The NM_002772.3(TMPRSS15):​c.345-1585C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,080 control chromosomes in the GnomAD database, including 957 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 0.11 (957 hom., cov: 32)
• Consequence: TMPRSS15 NM_002772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS15	NM_002772.3	c.345-1585C>T		intron_variant		ENST00000284885.8	NP_002763.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS15	ENST00000284885.8	c.345-1585C>T		intron_variant		1	NM_002772.3	ENSP00000284885.3
TMPRSS15	ENST00000422787.1	c.210-1585C>T		intron_variant		5		ENSP00000398253.1
TMPRSS15	ENST00000474775.1	c.-277-1585C>T		intron_variant		5		ENSP00000474811.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16429 AN: 151960 Hom.: 955 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.0669

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.108 AC: 16447 AN: 152080 Hom.: 957 Cov.: 32 AF XY: 0.106 AC XY: 7908 AN XY: 74324

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0678

Gnomad4 ASJ AF: 0.0891

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0988

Alfa AF: 0.108 Hom.: 1201

Bravo AF: 0.103

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.42
DANN	Benign	0.30

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: rs2824791; hg19: chr21-19757680;