rs112453913

Variant summary

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

The NM_004262.3(TMPRSS11D):​c.1216A>T​(p.Thr406Ser) 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 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T406A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMPRSS11D
NM_004262.3 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79
Variant links:
Genes affected
TMPRSS11D (HGNC:24059): (transmembrane serine protease 11D) This gene encodes a trypsin-like serine protease released from the submucosal serous glands onto mucous membrane. It is a type II integral membrane protein and has 29-38% identity in the sequence of the catalytic region with human hepsin, enteropeptidase, acrosin, and mast cell tryptase. The noncatalytic region has little similarity to other known proteins. This protein may play some biological role in the host defense system on the mucous membrane independently of or in cooperation with other substances in airway mucous or bronchial secretions. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. [provided by RefSeq, Aug 2021]
UBA6-DT (HGNC:49083): (UBA6 divergent transcript)

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ACMG classification

Classification made for transcript

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
TMPRSS11DNM_004262.3 linkc.1216A>T p.Thr406Ser missense_variant Exon 10 of 10 ENST00000283916.11 NP_004253.1 O60235
TMPRSS11DXM_017008851.2 linkc.664A>T p.Thr222Ser missense_variant Exon 6 of 6 XP_016864340.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMPRSS11DENST00000283916.11 linkc.1216A>T p.Thr406Ser missense_variant Exon 10 of 10 1 NM_004262.3 ENSP00000283916.6 O60235

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461638
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727108
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:
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
0.16
BayesDel_addAF
Benign
-0.00082
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
20
DANN
Benign
0.94
DEOGEN2
Uncertain
0.78
D
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.18
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.86
D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.46
T
MetaSVM
Benign
-0.31
T
MutationAssessor
Benign
-0.73
N
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.6
D
REVEL
Uncertain
0.33
Sift
Uncertain
0.019
D
Sift4G
Uncertain
0.028
D
Polyphen
0.92
P
Vest4
0.12
MutPred
0.62
Gain of glycosylation at Y402 (P = 0.0823);
MVP
0.82
MPC
0.42
ClinPred
0.94
D
GERP RS
1.7
Varity_R
0.20
gMVP
0.67

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: chr4-68688096; API