19-2426039-C-G

Variant names:

• chr19-2426039-C-G
• NM_001395513.1:c.3233C>G

Variant summary

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

The NM_001395513.1(TMPRSS9):​c.3233C>G​(p.Thr1078Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,924 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMPRSS9 NM_001395513.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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]

TIMM13 (HGNC:11816): (translocase of inner mitochondrial membrane 13) This gene encodes a member of the evolutionarily conserved TIMM (translocase of inner mitochondrial membrane) family of proteins that function as chaperones in the import of proteins from the cytoplasm into the mitochondrial inner membrane. Proteins of this family play a role in collecting substrate proteins from the translocase of the outer mitochondrial membrane (TOM) complex and delivering them to either the sorting and assembly machinery in the outer mitochondrial membrane (SAM) complex or the TIMM22 complex in the inner mitochondrial membrane. The encoded protein and the translocase of mitochondrial inner membrane 8a protein form a 70 kDa complex in the intermembrane space. [provided by RefSeq, Jul 2013]

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 rank	MANE	Protein	UniProt
TMPRSS9	NM_001395513.1	c.3233C>G	p.Thr1078Ser	missense_variant	Exon 19 of 19	ENST00000696167.1	NP_001382442.1
TIMM13	NM_012458.4	c.*909G>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000215570.8	NP_036590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS9	ENST00000696167.1	c.3233C>G	p.Thr1078Ser	missense_variant	Exon 19 of 19		NM_001395513.1	ENSP00000512457.1
TIMM13	ENST00000215570	c.*909G>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_012458.4	ENSP00000215570.2
TMPRSS9	ENST00000648592.1	c.3233C>G	p.Thr1078Ser	missense_variant	Exon 18 of 18			ENSP00000498031.1
TMPRSS9	ENST00000649857.1	c.3131C>G	p.Thr1044Ser	missense_variant	Exon 18 of 18			ENSP00000497651.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456924 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724906

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;T
Eigen	Benign	0.040
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.1	M;.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	.;.;N
REVEL	Uncertain	0.41
Sift	Benign	0.18	.;.;T
Sift4G	Benign	0.15	.;.;T
Polyphen		0.23	B;.;B
Vest4		0.39
MutPred		0.77		Gain of glycosylation at T1044 (P = 0.032);.;Gain of glycosylation at T1044 (P = 0.032);
MVP		0.90
MPC		0.21
ClinPred		0.80	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.55

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: chr19-2426037;