rs4806846

Positions:

• chr19-2410486-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395513.1(TMPRSS9):​c.1254+92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,501,352 control chromosomes in the GnomAD database, including 19,735 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 0.13 (2006 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17729 hom.)
• Consequence: TMPRSS9 NM_001395513.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

Genes affected

TMPRSS9 (HGNC:30079): (transmembrane serine protease 9) The protein encoded by this gene is a membrane-bound type II serine polyprotease that is cleaved to release three different proteases. Two of the proteases are active and can be inhibited by serine protease inhibitors, and one is thought to be catalytically inactive. This gene enhances the invasive capability of pancreatic cancer cells and may be involved in cancer progression. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1	c.1254+92G>A		intron_variant		ENST00000696167.1	NP_001382442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS9	ENST00000696167.1	c.1254+92G>A		intron_variant			NM_001395513.1	ENSP00000512457.1
TMPRSS9	ENST00000395264.3	n.1269+92G>A		intron_variant		1
TMPRSS9	ENST00000648592.1	c.1254+92G>A		intron_variant				ENSP00000498031.1
TMPRSS9	ENST00000649857.1	c.1152+92G>A		intron_variant				ENSP00000497651.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20402 AN: 151894 Hom.: 1996 Cov.: 31

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.151 AC: 203302 AN: 1349340 Hom.: 17729 AF XY: 0.149 AC XY: 99275 AN XY: 664164

Gnomad4 AFR exome AF: 0.0242

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.134 AC: 20429 AN: 152012 Hom.: 2006 Cov.: 31 AF XY: 0.142 AC XY: 10520 AN XY: 74290

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.134

Alfa AF: 0.134 Hom.: 201

Bravo AF: 0.141

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs4806846; hg19: chr19-2410484; COSMIC: COSV60225544;