chr19-2396614-G-C

Variant names:

• chr19-2396614-G-C
• NM_001395513.1:c.218G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395513.1(TMPRSS9):​c.218G>C​(p.Arg73Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMPRSS9 NM_001395513.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13886765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1	c.218G>C	p.Arg73Pro	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.218G>C	p.Arg73Pro	missense_variant	Exon 3 of 19		NM_001395513.1	ENSP00000512457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451754 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721526

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000471

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0041	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	6.5
DANN	Benign	0.76
DEOGEN2	Benign	0.0046	T;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.66	.;T;T;T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.34	N;.;.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.0	.;.;.;N
REVEL	Benign	0.26
Sift	Uncertain	0.0030	.;.;.;D
Sift4G	Uncertain	0.0050	.;.;D;D
Polyphen		0.12	B;.;.;B
Vest4		0.32, 0.33
MutPred		0.31		Loss of MoRF binding (P = 0.0075);Loss of MoRF binding (P = 0.0075);Loss of MoRF binding (P = 0.0075);Loss of MoRF binding (P = 0.0075);
MVP		0.58
MPC		0.13
ClinPred		0.35	T
GERP RS		0.56
Varity_R		0.22
gMVP		0.33

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: chr19-2396612;