rs2258447

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018406.7(MUC4):​c.15570A>T​(p.Glu5190Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 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 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MUC4
NM_018406.7 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39
Variant links:
Genes affected
MUC4 (HGNC:7514): (mucin 4, cell surface associated) The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.021777004).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MUC4NM_018406.7 linkuse as main transcriptc.15570A>T p.Glu5190Asp missense_variant 21/25 ENST00000463781.8
MUC4NM_004532.6 linkuse as main transcriptc.2862A>T p.Glu954Asp missense_variant 20/24
MUC4NM_138297.5 linkuse as main transcriptc.2709A>T p.Glu903Asp missense_variant 19/23

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MUC4ENST00000463781.8 linkuse as main transcriptc.15570A>T p.Glu5190Asp missense_variant 21/255 NM_018406.7 A2Q99102-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152170
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461532
Hom.:
0
Cov.:
55
AF XY:
0.00000138
AC XY:
1
AN XY:
727108
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152170
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.057
DANN
Benign
0.33
Eigen
Benign
-2.7
Eigen_PC
Benign
-2.7
FATHMM_MKL
Benign
0.0064
N
LIST_S2
Benign
0.48
T;T;T;T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.022
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
P;P;P;P
PrimateAI
Benign
0.36
T
PROVEAN
Benign
1.3
N;N;N;N
REVEL
Benign
0.023
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0020
B;B;B;B
Vest4
0.036
MutPred
0.36
.;.;Loss of disorder (P = 0.1365);.;
MVP
0.014
ClinPred
0.055
T
GERP RS
-9.5
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2258447; hg19: chr3-195479256; API