Variant rs15783 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135091.2(MUC15):c.686C>T(p.Thr229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,583,798 control chromosomes in the GnomAD database, including 332,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 29615 hom., cov: 31)

Exomes 𝑓: 0.65 ( 302962 hom. )

Consequence

MUC15
NM_001135091.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3498485E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC15	NM_001135091.2 linkuse as main transcript	c.686C>T	p.Thr229Ile	missense_variant	3/5	ENST00000529533.6	NP_001128563.1	Q8N387A0A0A0MT67
ANO3	NM_031418.4 linkuse as main transcript	c.1447+5475G>A		intron_variant		ENST00000256737.8	NP_113606.2	Q9BYT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC15	ENST00000529533.6 linkuse as main transcript	c.686C>T	p.Thr229Ile	missense_variant	3/5	1	NM_001135091.2	ENSP00000431983.1		A0A0A0MT67
ANO3	ENST00000256737.8 linkuse as main transcript	c.1447+5475G>A		intron_variant		1	NM_031418.4	ENSP00000256737.3		Q9BYT9-1

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

93776

AN:

151506

Hom.:

29616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.687

Gnomad AMR

AF:

0.727

Gnomad ASJ

AF:

0.657

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.749

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.630

GnomAD3 exomes

AF:

0.643

AC:

149330

AN:

232186

Hom.:

49273

AF XY:

0.640

AC XY:

79956

AN XY:

124866

show subpopulations

Gnomad AFR exome

AF:

0.510

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.432

Gnomad SAS exome

AF:

0.580

Gnomad FIN exome

AF:

0.744

Gnomad NFE exome

AF:

0.644

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.647

AC:

927123

AN:

1432174

Hom.:

302962

Cov.:

AF XY:

0.646

AC XY:

457898

AN XY:

709180

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.797

Gnomad4 ASJ exome

AF:

0.663

Gnomad4 EAS exome

AF:

0.406

Gnomad4 SAS exome

AF:

0.590

Gnomad4 FIN exome

AF:

0.736

Gnomad4 NFE exome

AF:

0.654

Gnomad4 OTH exome

AF:

0.642

GnomAD4 genome

AF:

0.619

AC:

93797

AN:

151624

Hom.:

29615

Cov.:

AF XY:

0.625

AC XY:

46303

AN XY:

74124

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.726

Gnomad4 ASJ

AF:

0.657

Gnomad4 EAS

AF:

0.444

Gnomad4 SAS

AF:

0.571

Gnomad4 FIN

AF:

0.749

Gnomad4 NFE

AF:

0.649

Gnomad4 OTH

AF:

0.624

Alfa

AF:

0.636

Hom.:

54599

Bravo

AF:

0.617

TwinsUK

AF:

0.665

AC:

2467

ALSPAC

AF:

0.662

AC:

2552

ESP6500AA

AF:

0.515

AC:

2268

ESP6500EA

AF:

0.648

AC:

5573

ExAC

AF:

0.632

AC:

76628

Asia WGS

AF:

0.504

AC:

1754

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T;T;T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.70

T;T;T;.;.;T

MetaRNN

Benign

0.0000013

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;.;L;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.0

D;D;D;D;D;.

REVEL

Benign

0.036

Sift

Benign

0.057

T;D;T;T;D;.

Sift4G

Uncertain

0.0060

D;D;D;D;D;.

Polyphen

0.49

.;.;P;.;.;.

Vest4

0.076

MPC

0.17

ClinPred

0.037

GERP RS

2.1

Varity_R

0.13

gMVP

0.60

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.

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