rs2824724

Variant names:

• chr21-18302364-G-A
• rs2824724
• NM_002772.3:c.2166-4535C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002772.3(TMPRSS15):​c.2166-4535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,018 control chromosomes in the GnomAD database, including 46,070 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 0.78 (46070 hom., cov: 30)
• Consequence: TMPRSS15 NM_002772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 6 publications found

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]

TMPRSS15 Gene-Disease associations (from GenCC):

• congenital enteropathy due to enteropeptidase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS15	NM_002772.3	c.2166-4535C>T		intron_variant	Intron 18 of 24	ENST00000284885.8	NP_002763.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS15	ENST00000284885.8	c.2166-4535C>T		intron_variant	Intron 18 of 24	1	NM_002772.3	ENSP00000284885.3

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118098 AN: 151900 Hom.: 46021 Cov.: 30

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.778 AC: 118201 AN: 152018 Hom.: 46070 Cov.: 30 AF XY: 0.777 AC XY: 57728 AN XY: 74312

African (AFR) AF: 0.801 AC: 33201 AN: 41470

American (AMR) AF: 0.743 AC: 11337 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2501 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3407 AN: 5152

South Asian (SAS) AF: 0.718 AC: 3447 AN: 4804

European-Finnish (FIN) AF: 0.809 AC: 8554 AN: 10574

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53381 AN: 67974

Other (OTH) AF: 0.766 AC: 1617 AN: 2110

Alfa AF: 0.775 Hom.: 45867

Bravo AF: 0.770

Asia WGS AF: 0.702 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.051
DANN	Benign	0.46
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2824724; hg19: chr21-19674681;