19-2363321-C-T

Position:

• chr19-2363321-C-T

Variant summary

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

The NM_001395513.1(TMPRSS9):​c.-26+2961C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,944 control chromosomes in the GnomAD database, including 9,430 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 0.34 (9430 hom., cov: 32)
• Consequence: TMPRSS9 NM_001395513.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1	c.-26+2961C>T		intron_variant		ENST00000696167.1	NP_001382442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS9	ENST00000696167.1	c.-26+2961C>T		intron_variant			NM_001395513.1	ENSP00000512457	P1
TMPRSS9	ENST00000649857.1	c.-26+2961C>T		intron_variant				ENSP00000497651

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52230 AN: 151826 Hom.: 9412 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.344 AC: 52290 AN: 151944 Hom.: 9430 Cov.: 32 AF XY: 0.352 AC XY: 26132 AN XY: 74262

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.347

Alfa AF: 0.185 Hom.: 365

Bravo AF: 0.353

Asia WGS AF: 0.500 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62120679; hg19: chr19-2363319;