4-68461891-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014058.4(TMPRSS11E):​c.82T>A​(p.Ser28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TMPRSS11E
NM_014058.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25
Variant links:
Genes affected
TMPRSS11E (HGNC:24465): (transmembrane serine protease 11E) Predicted to enable serine-type peptidase activity. Involved in cognition. Predicted to be integral component of plasma membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.35402328).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMPRSS11ENM_014058.4 linkc.82T>A p.Ser28Thr missense_variant Exon 2 of 10 ENST00000305363.9 NP_054777.2 Q9UL52
TMPRSS11EXM_047450139.1 linkc.-153T>A 5_prime_UTR_variant Exon 2 of 10 XP_047306095.1
TMPRSS11EXM_011531896.3 linkc.-98-4740T>A intron_variant Intron 1 of 8 XP_011530198.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMPRSS11EENST00000305363.9 linkc.82T>A p.Ser28Thr missense_variant Exon 2 of 10 1 NM_014058.4 ENSP00000307519.4 Q9UL52
TMPRSS11EENST00000510647.1 linkn.70T>A non_coding_transcript_exon_variant Exon 1 of 6 3 ENSP00000424109.1 H0Y9G7

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152220
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.82T>A (p.S28T) alteration is located in exon 2 (coding exon 2) of the TMPRSS11E gene. This alteration results from a T to A substitution at nucleotide position 82, causing the serine (S) at amino acid position 28 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
0.0048
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
18
DANN
Benign
0.91
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.059
Eigen_PC
Benign
-0.068
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.35
T
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.23
Sift
Benign
0.13
T
Sift4G
Benign
0.20
T
Polyphen
0.75
P
Vest4
0.41
MutPred
0.36
Loss of glycosylation at S28 (P = 0.0342);
MVP
0.83
MPC
0.34
ClinPred
0.45
T
GERP RS
6.0
Varity_R
0.098
gMVP
0.45

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: rs1292394947; hg19: chr4-69327609; API