19-2399095-T-G

Variant names:

• chr19-2399095-T-G
• NM_001395513.1:c.416T>G

Variant summary

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

The NM_001395513.1(TMPRSS9):​c.416T>G​(p.Leu139Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMPRSS9 NM_001395513.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936

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=0.2993078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1	c.416T>G	p.Leu139Arg	missense_variant	Exon 5 of 19	ENST00000696167.1	NP_001382442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS9	ENST00000696167.1	c.416T>G	p.Leu139Arg	missense_variant	Exon 5 of 19		NM_001395513.1	ENSP00000512457.1
TMPRSS9	ENST00000395264.3	n.431T>G		non_coding_transcript_exon_variant	Exon 4 of 10	1
TMPRSS9	ENST00000648592.1	c.416T>G	p.Leu139Arg	missense_variant	Exon 4 of 18			ENSP00000498031.1
TMPRSS9	ENST00000649857.1	c.314T>G	p.Leu105Arg	missense_variant	Exon 4 of 18			ENSP00000497651.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461416 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726976

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

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	0.071
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0085	T;.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.49	.;T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.0	M;.;.;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.2	.;.;.;N
REVEL	Uncertain	0.39
Sift	Benign	0.050	.;.;.;D
Sift4G	Benign	0.086	.;.;T;T
Polyphen		0.69	P;.;.;P
Vest4		0.61, 0.54
MutPred		0.47		Gain of methylation at L105 (P = 0.0217);.;Gain of methylation at L105 (P = 0.0217);Gain of methylation at L105 (P = 0.0217);
MVP		0.90
MPC		0.20
ClinPred		0.32	T
GERP RS		2.2
Varity_R		0.071
gMVP		0.61

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: chr19-2399093;