4-68228800-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182502.3(TMPRSS11B):​c.1031T>G​(p.Phe344Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TMPRSS11B
NM_182502.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.446
Variant links:
Genes affected
TMPRSS11B (HGNC:25398): (transmembrane serine protease 11B) Enables serine-type peptidase activity. Predicted to be involved in proteolysis. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23963761).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMPRSS11BNM_182502.3 linkc.1031T>G p.Phe344Cys missense_variant 9/10 ENST00000332644.6 NP_872308.2 Q86T26
TMPRSS11BXM_011531608.3 linkc.1031T>G p.Phe344Cys missense_variant 9/11 XP_011529910.1 Q86T26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMPRSS11BENST00000332644.6 linkc.1031T>G p.Phe344Cys missense_variant 9/101 NM_182502.3 ENSP00000330475.5 Q86T26
TMPRSS11BENST00000510856.1 linkn.507T>G non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
41
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2023The c.1031T>G (p.F344C) alteration is located in exon 9 (coding exon 9) of the TMPRSS11B gene. This alteration results from a T to G substitution at nucleotide position 1031, causing the phenylalanine (F) at amino acid position 344 to be replaced by a cysteine (C). 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
0.20
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
2.0
DANN
Benign
0.67
DEOGEN2
Benign
0.24
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.19
T
M_CAP
Uncertain
0.089
D
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.20
N
REVEL
Uncertain
0.33
Sift
Benign
0.19
T
Sift4G
Benign
0.20
T
Polyphen
0.34
B
Vest4
0.25
MutPred
0.52
Loss of glycosylation at S342 (P = 0.0144);
MVP
0.25
MPC
0.068
ClinPred
0.21
T
GERP RS
-2.4
Varity_R
0.056
gMVP
0.52

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: chr4-69094518; API