19-2396568-G-C

Variant names:

• chr19-2396568-G-C
• NM_001395513.1:c.172G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395513.1(TMPRSS9):​c.172G>C​(p.Asp58His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMPRSS9 NM_001395513.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34529644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1	c.172G>C	p.Asp58His	missense_variant	Exon 3 of 19	ENST00000696167.1	NP_001382442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS9	ENST00000696167.1	c.172G>C	p.Asp58His	missense_variant	Exon 3 of 19		NM_001395513.1	ENSP00000512457.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.172G>C (p.D58H) alteration is located in exon 2 (coding exon 2) of the TMPRSS9 gene. This alteration results from a G to C substitution at nucleotide position 172, causing the aspartic acid (D) at amino acid position 58 to be replaced by a histidine (H). 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	0.16
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T;.;.;T
Eigen	Benign	0.031
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	.;T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	0.90	L;.;.;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	.;.;.;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	.;.;.;D
Sift4G	Uncertain	0.012	.;.;D;T
Polyphen		0.64	P;.;.;P
Vest4		0.35, 0.34
MutPred		0.47		Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);
MVP		0.85
MPC		0.25
ClinPred		0.73	D
GERP RS		4.0
Varity_R		0.19
gMVP		0.28

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: chr19-2396566;