NM_001428056.1:c.-172-9493C>A

Variant names:

• chr21-18415699-G-T
• rs2225408
• NM_001428056.1:c.-172-9493C>A

Variant summary

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

The NM_001428056.1(TMPRSS15):​c.-172-9493C>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 NM_001428056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 1 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=-1.07).
• BA1: GnomAd4 highest subpopulation (AMR) 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.-172-9493C>A		intron	N/A	NP_001414985.1
	TMPRSS15	NM_001428057.1		c.-172-9493C>A		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.11-17370C>A		intron	N/A	ENSP00000398253.1
	TMPRSS15	ENST00000474775.1	TSL:5	c.-277-31921C>A		intron	N/A	ENSP00000474811.1

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

African (AFR) AF: 0.576 AC: 23851 AN: 41416

American (AMR) AF: 0.689 AC: 10511 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2532 AN: 3466

East Asian (EAS) AF: 0.594 AC: 3064 AN: 5162

South Asian (SAS) AF: 0.618 AC: 2979 AN: 4822

European-Finnish (FIN) AF: 0.629 AC: 6627 AN: 10540

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.688 AC: 46665 AN: 67854

Other (OTH) AF: 0.666 AC: 1399 AN: 2100

Alfa AF: 0.667 Hom.: 4433

Bravo AF: 0.653

Asia WGS AF: 0.540 AC: 1875 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.39
DANN	Benign	0.34
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs2225408; hg19: chr21-19788016;