dbSNP rs759346265: MUC15:p.Ala315Val (chr11-26561207-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001135091.2(MUC15):c.944C>T(p.Ala315Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A315E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MUC15
NM_001135091.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.00

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]

MUC15 links:

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]

ANO3 links:

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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=0.25971812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC15	NM_001135091.2 link	c.944C>T	p.Ala315Val	missense_variant	Exon 5 of 5	ENST00000529533.6	NP_001128563.1	Q8N387A0A0A0MT67
ANO3	NM_031418.4 link	c.1447+1428G>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
MUC15	ENST00000529533.6 link	c.944C>T	p.Ala315Val	missense_variant	Exon 5 of 5	1	NM_001135091.2	ENSP00000431983.1		A0A0A0MT67
ANO3	ENST00000256737.8 link	c.1447+1428G>A		intron_variant	Intron 14 of 26	1	NM_031418.4	ENSP00000256737.3		Q9BYT9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246038

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133172

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456684

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

T;T;T;T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

T;T;T;.;.

M_CAP

Benign

0.026

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.97

.;.;L;.;.

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.035

Sift

Uncertain

0.0050

D;D;D;D;D

Sift4G

Uncertain

0.027

D;D;D;D;D

Polyphen

0.74

.;.;P;.;.

Vest4

0.14

MutPred

0.43

.;.;Loss of disorder (P = 0.1738);.;.;

MVP

0.21

MPC

0.15

ClinPred

0.95

GERP RS

4.5

Varity_R

0.22

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over