NM_002458.3:c.158T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002458.3(MUC5B):​c.158T>C​(p.Val53Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000708 in 1,553,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.857

Publications

0 publications found
Variant links:
Genes affected
MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]
MUC5B Gene-Disease associations (from GenCC):
  • interstitial lung disease
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09092313).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MUC5BNM_002458.3 linkc.158T>C p.Val53Ala missense_variant Exon 3 of 49 ENST00000529681.5 NP_002449.2 Q9HC84

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MUC5BENST00000529681.5 linkc.158T>C p.Val53Ala missense_variant Exon 3 of 49 5 NM_002458.3 ENSP00000436812.1 Q9HC84
MUC5BENST00000525715.5 linkn.216T>C non_coding_transcript_exon_variant Exon 3 of 26 1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152134
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000571
AC:
8
AN:
1401642
Hom.:
0
Cov.:
33
AF XY:
0.00000289
AC XY:
2
AN XY:
692384
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31724
American (AMR)
AF:
0.00
AC:
0
AN:
36830
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25256
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35964
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79462
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46954
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5708
European-Non Finnish (NFE)
AF:
0.00000740
AC:
8
AN:
1081562
Other (OTH)
AF:
0.00
AC:
0
AN:
58182
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152134
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74332
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41418
American (AMR)
AF:
0.0000654
AC:
1
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
67998
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.642
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000780
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 17, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.158T>C (p.V53A) alteration is located in exon 3 (coding exon 3) of the MUC5B gene. This alteration results from a T to C substitution at nucleotide position 158, causing the valine (V) at amino acid position 53 to be replaced by an alanine (A). 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
0.12
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
15
DANN
Benign
0.61
DEOGEN2
Benign
0.028
T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.28
T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L
PhyloP100
-0.86
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.024
Sift
Benign
0.047
D
Polyphen
0.23
B
Vest4
0.15
MutPred
0.25
Loss of sheet (P = 0.0025);
MVP
0.043
ClinPred
0.095
T
GERP RS
2.0
Varity_R
0.096
gMVP
0.84
Mutation Taster
=97/3
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs867713996; hg19: chr11-1247465; API