rs200696532

Variant summary

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

The NM_001135091.2(MUC15):​c.946C>T​(p.Pro316Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,609,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. P316T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MUC15
NM_001135091.2 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71
Variant links:
Genes affected
MUC15 (HGNC:14956): (mucin 15, cell surface associated) Predicted to be located in Golgi lumen and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
ANO3 (HGNC:14004): (anoctamin 3) The protein encoded by this gene belongs to the TMEM16 family of predicted membrane proteins, that are also known as anoctamins. While little is known about the function of this gene, mutations in this gene have been associated with some cases of autosomal dominant craniocervical dystonia. Cells from individuals with a mutation in this gene exhibited abnormalities in endoplasmic reticulum-dependent calcium signaling. Studies in rat show that the rat ortholog of this protein interacts with, and modulates the activity of a sodium-activated potassium channel. Deletion of this gene caused increased pain sensitivity in the rat model system. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

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=0.010944456).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MUC15NM_001135091.2 linkc.946C>T p.Pro316Ser missense_variant Exon 5 of 5 ENST00000529533.6 NP_001128563.1 Q8N387A0A0A0MT67
ANO3NM_031418.4 linkc.1447+1426G>A intron_variant Intron 14 of 26 ENST00000256737.8 NP_113606.2 Q9BYT9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MUC15ENST00000529533.6 linkc.946C>T p.Pro316Ser missense_variant Exon 5 of 5 1 NM_001135091.2 ENSP00000431983.1 A0A0A0MT67
ANO3ENST00000256737.8 linkc.1447+1426G>A intron_variant Intron 14 of 26 1 NM_031418.4 ENSP00000256737.3 Q9BYT9-1

Frequencies

GnomAD3 genomes
AF:
0.0000527
AC:
8
AN:
151940
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:
0.00155
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
GnomAD3 exomes
AF:
0.000231
AC:
57
AN:
246780
Hom.:
1
AF XY:
0.000262
AC XY:
35
AN XY:
133540
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00298
Gnomad SAS exome
AF:
0.0000666
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.0000439
AC:
64
AN:
1457354
Hom.:
0
Cov.:
30
AF XY:
0.0000483
AC XY:
35
AN XY:
724908
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00135
Gnomad4 SAS exome
AF:
0.0000702
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152058
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00155
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.000102
ExAC
AF:
0.000239
AC:
29
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.099
T;T;T;T;T
Eigen
Benign
0.092
Eigen_PC
Benign
0.15
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.70
T;T;T;.;.
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.011
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
.;.;N;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-4.0
D;D;D;D;D
REVEL
Benign
0.070
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Benign
0.22
T;T;T;T;T
Polyphen
0.74
.;.;P;.;.
Vest4
0.094
MVP
0.22
MPC
0.17
ClinPred
0.23
T
GERP RS
2.4
Varity_R
0.34
gMVP
0.62

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: rs200696532; hg19: chr11-26582752; API