rs202221607

Variant names:

• chr19-2396595-C-A
• rs202221607
• NM_001395513.1:c.199C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-2396595-C-A
• chr19-2396595-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001395513.1(TMPRSS9):​c.199C>A​(p.Arg67Arg) variant causes a synonymous 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: 33)
• Consequence: TMPRSS9 NM_001395513.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 2 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.052 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395513.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS9	NM_001395513.1	MANE Select	c.199C>A	p.Arg67Arg	synonymous	Exon 3 of 19	NP_001382442.1	A0A3B3IU58
	TMPRSS9	NM_182973.3		c.199C>A	p.Arg67Arg	synonymous	Exon 3 of 18	NP_892018.1	Q7Z410
	TMPRSS9	NM_001385642.1		c.-498C>A		5_prime_UTR	Exon 2 of 18	NP_001372571.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS9	ENST00000696167.1	MANE Select	c.199C>A	p.Arg67Arg	synonymous	Exon 3 of 19	ENSP00000512457.1	A0A3B3IU58
	TMPRSS9	ENST00000395264.3	TSL:1	n.214C>A		non_coding_transcript_exon	Exon 2 of 10
	TMPRSS9	ENST00000648592.1		c.199C>A	p.Arg67Arg	synonymous	Exon 2 of 18	ENSP00000498031.1	A0A3B3IU58

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.9
DANN	Benign	0.61
PhyloP100		-0.052

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: rs202221607; hg19: chr19-2396593;