rs293979

Variant names:

• chr11-26565803-G-A
• rs293979
• NM_001135091.2:c.137C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-26565803-G-A
• chr11-26565803-G-C
• chr11-26565803-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135091.2(MUC15):​c.137C>T​(p.Ser46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,611,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. S46W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: MUC15 NM_001135091.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050214887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.137C>T	p.Ser46Leu	missense_variant	Exon 3 of 5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+6024G>A		intron_variant	Intron 14 of 26	ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC15	ENST00000529533.6	c.137C>T	p.Ser46Leu	missense_variant	Exon 3 of 5	1	NM_001135091.2	ENSP00000431983.1
ANO3	ENST00000256737.8	c.1447+6024G>A		intron_variant	Intron 14 of 26	1	NM_031418.4	ENSP00000256737.3

Frequencies

GnomAD3 genomes AF: 0.0000400 AC: 6 AN: 150182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

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

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250414 AF XY: 0.0000369

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461094 Hom.: 0 Cov.: 34 AF XY: 0.0000165 AC XY: 12 AN XY: 726846

African (AFR) AF: 0.0000898 AC: 3 AN: 33426

American (AMR) AF: 0.0000896 AC: 4 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39676

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111514

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome AF: 0.0000399 AC: 6 AN: 150300 Hom.: 0 Cov.: 33 AF XY: 0.0000272 AC XY: 2 AN XY: 73558

African (AFR) AF: 0.000121 AC: 5 AN: 41332

American (AMR) AF: 0.0000662 AC: 1 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66756

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000793

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.66
DANN	Benign	0.72
DEOGEN2	Benign	0.013	T;T;T;T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00073	N
LIST_S2	Benign	0.64	T;T;T;.;.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.050	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;.;N;.;.;.
PhyloP100		-0.045
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.58	N;N;N;N;N;.
REVEL	Benign	0.0090
Sift	Benign	0.70	T;T;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;.
Polyphen		0.0010	.;.;B;.;.;.
Vest4		0.075
MutPred		0.22		.;.;Loss of disorder (P = 0.0138);.;.;.;
MVP		0.014
MPC		0.021
ClinPred		0.014	T
GERP RS		0.86
Varity_R		0.024
gMVP		0.083
Mutation Taster		=96/4	polymorphism

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs293979; hg19: chr11-26587350; COSMIC: COSV55554858; COSMIC: COSV55554858;