rs7252121

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001395513.1(TMPRSS9):​c.3233C>A​(p.Thr1078Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TMPRSS9
NM_001395513.1 missense

Scores

8
9
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.02
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.931

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMPRSS9NM_001395513.1 linkc.3233C>A p.Thr1078Asn missense_variant Exon 19 of 19 ENST00000696167.1 NP_001382442.1
TIMM13NM_012458.4 linkc.*909G>T 3_prime_UTR_variant Exon 3 of 3 ENST00000215570.8 NP_036590.1 Q9Y5L4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMPRSS9ENST00000696167.1 linkc.3233C>A p.Thr1078Asn missense_variant Exon 19 of 19 NM_001395513.1 ENSP00000512457.1 A0A3B3IU58
TIMM13ENST00000215570 linkc.*909G>T 3_prime_UTR_variant Exon 3 of 3 1 NM_012458.4 ENSP00000215570.2 Q9Y5L4
TMPRSS9ENST00000648592.1 linkc.3233C>A p.Thr1078Asn missense_variant Exon 18 of 18 ENSP00000498031.1 A0A3B3IU58
TMPRSS9ENST00000649857.1 linkc.3131C>A p.Thr1044Asn missense_variant Exon 18 of 18 ENSP00000497651.1 Q7Z410

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000409
AC:
1
AN:
244376
Hom.:
0
AF XY:
0.00000752
AC XY:
1
AN XY:
132972
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000913
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456924
Hom.:
0
Cov.:
31
AF XY:
0.00000414
AC XY:
3
AN XY:
724906
show subpopulations
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:
0.00000270
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
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.39
T;.;T
Eigen
Pathogenic
0.72
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
.;D;D
M_CAP
Pathogenic
0.44
D
MetaRNN
Pathogenic
0.93
D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.4
M;.;M
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-2.9
.;.;D
REVEL
Pathogenic
0.82
Sift
Uncertain
0.0020
.;.;D
Sift4G
Uncertain
0.0050
.;.;D
Polyphen
1.0
D;.;D
Vest4
0.80
MutPred
0.83
Gain of MoRF binding (P = 0.1221);.;Gain of MoRF binding (P = 0.1221);
MVP
0.96
MPC
0.46
ClinPred
0.98
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.79
gMVP
0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7252121; hg19: chr19-2426037; API