21-18416800-T-C

Variant names:

• chr21-18416800-T-C
• rs2824814
• NM_001428056.1:c.-172-10594A>G

Variant summary

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

The NM_001428056.1(TMPRSS15):​c.-172-10594A>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 NM_001428056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001428056.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS15	NM_001428056.1		c.-172-10594A>G		intron	N/A	NP_001414985.1
	TMPRSS15	NM_001428057.1		c.-172-10594A>G		intron	N/A	NP_001414986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS15	ENST00000422787.1	TSL:5	c.11-18471A>G		intron	N/A	ENSP00000398253.1
	TMPRSS15	ENST00000474775.1	TSL:5	c.-277-33022A>G		intron	N/A	ENSP00000474811.1

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

African (AFR) AF: 0.538 AC: 22282 AN: 41432

American (AMR) AF: 0.685 AC: 10458 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2536 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3082 AN: 5142

South Asian (SAS) AF: 0.617 AC: 2975 AN: 4818

European-Finnish (FIN) AF: 0.626 AC: 6614 AN: 10562

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.687 AC: 46579 AN: 67794

Other (OTH) AF: 0.655 AC: 1379 AN: 2104

Alfa AF: 0.674 Hom.: 19105

Bravo AF: 0.641

Asia WGS AF: 0.540 AC: 1873 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.81
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs2824814; hg19: chr21-19789117;