chr21-18385363-G-A

Variant names:

• chr21-18385363-G-A
• rs2824791
• NM_002772.3:c.345-1585C>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.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
• 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=-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 rank	MANE	Protein	UniProt
TMPRSS15	NM_002772.3	c.345-1585C>T		intron_variant	Intron 3 of 24	ENST00000284885.8	NP_002763.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS15	ENST00000284885.8	c.345-1585C>T		intron_variant	Intron 3 of 24	1	NM_002772.3	ENSP00000284885.3
TMPRSS15	ENST00000422787.1	c.210-1585C>T		intron_variant	Intron 3 of 7	5		ENSP00000398253.1
TMPRSS15	ENST00000474775.1	c.-277-1585C>T		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.130 AC: 5390 AN: 41480

American (AMR) AF: 0.0678 AC: 1036 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 309 AN: 3468

East Asian (EAS) AF: 0.0124 AC: 64 AN: 5170

South Asian (SAS) AF: 0.0667 AC: 322 AN: 4826

European-Finnish (FIN) AF: 0.130 AC: 1375 AN: 10558

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7700 AN: 67978

Other (OTH) AF: 0.0988 AC: 208 AN: 2106

Alfa AF: 0.108 Hom.: 1519

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
PhyloP100		-1.7
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: rs2824791; hg19: chr21-19757680;