rs2225408

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001428056.1(TMPRSS15):​c.-172-9493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS15	NM_001428056.1	c.-172-9493C>T		intron_variant	Intron 1 of 28		NP_001414985.1
TMPRSS15	NM_001428057.1	c.-172-9493C>T		intron_variant	Intron 1 of 26		NP_001414986.1
TMPRSS15	XM_047440912.1	c.-172-9493C>T		intron_variant	Intron 1 of 28		XP_047296868.1
TMPRSS15	XM_047440913.1	c.-172-9493C>T		intron_variant	Intron 1 of 26		XP_047296869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS15	ENST00000422787.1	c.11-17370C>T		intron_variant	Intron 1 of 7	5		ENSP00000398253.1
TMPRSS15	ENST00000474775.1	c.-277-31921C>T		intron_variant	Intron 1 of 3	5		ENSP00000474811.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.48
DANN	Benign	0.93
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;