chr19-2363321-C-T

Variant names:

• chr19-2363321-C-T
• rs62120679
• NM_001395513.1:c.-26+2961C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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]

TMPRSS9 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1	c.-26+2961C>T		intron_variant	Intron 1 of 18	ENST00000696167.1	NP_001382442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS9	ENST00000696167.1	c.-26+2961C>T		intron_variant	Intron 1 of 18		NM_001395513.1	ENSP00000512457.1
TMPRSS9	ENST00000649857.1	c.-26+2961C>T		intron_variant	Intron 1 of 17			ENSP00000497651.1

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

African (AFR) AF: 0.333 AC: 13800 AN: 41424

American (AMR) AF: 0.415 AC: 6340 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1185 AN: 3472

East Asian (EAS) AF: 0.662 AC: 3414 AN: 5160

South Asian (SAS) AF: 0.413 AC: 1986 AN: 4810

European-Finnish (FIN) AF: 0.327 AC: 3442 AN: 10538

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20792 AN: 67960

Other (OTH) AF: 0.347 AC: 733 AN: 2114

Alfa AF: 0.319 Hom.: 11501

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
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs62120679; hg19: chr19-2363319;