19-2399169-A-G

Position:

• chr19-2399169-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395513.1(TMPRSS9):​c.490A>G​(p.Thr164Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMPRSS9 NM_001395513.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1	c.490A>G	p.Thr164Ala	missense_variant	5/19	ENST00000696167.1	NP_001382442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS9	ENST00000696167.1	c.490A>G	p.Thr164Ala	missense_variant	5/19		NM_001395513.1	ENSP00000512457.1
TMPRSS9	ENST00000395264.3	n.505A>G		non_coding_transcript_exon_variant	4/10	1
TMPRSS9	ENST00000648592.1	c.490A>G	p.Thr164Ala	missense_variant	4/18			ENSP00000498031.1
TMPRSS9	ENST00000649857.1	c.388A>G	p.Thr130Ala	missense_variant	4/18			ENSP00000497651.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.388A>G (p.T130A) alteration is located in exon 3 (coding exon 3) of the TMPRSS9 gene. This alteration results from a A to G substitution at nucleotide position 388, causing the threonine (T) at amino acid position 130 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0053	T;.;.;T
Eigen	Benign	0.026
Eigen_PC	Benign	-0.0082
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.53	.;T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.4	M;.;.;M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	.;.;.;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.014	.;.;.;D
Sift4G	Uncertain	0.042	.;.;D;D
Polyphen		0.75	P;.;.;P
Vest4		0.36, 0.32
MutPred		0.36		Gain of sheet (P = 0.1945);.;Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);
MVP		0.85
MPC		0.078
ClinPred		0.74	D
GERP RS		3.3
Varity_R		0.12
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-2399167;