11-26559835-TACACACACACACACACACACACACACAC-TACACACACACACACACACACACACACACACACACAC

Variant names:

• chr11-26559835-T-TACACACAC
• rs71047866
• NM_001135091.2:c.*1222_*1229dupGTGTGTGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001135091.2(MUC15):​c.*1222_*1229dupGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 2 publications found

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]

ANO3 Gene-Disease associations (from GenCC):

• dystonia 24

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135091.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC15	NM_001135091.2	MANE Select	c.*1222_*1229dupGTGTGTGT		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1447+89_1447+96dupACACACAC		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1222_*1229dupGTGTGTGT		3_prime_UTR	Exon 4 of 4	NP_663625.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC15	ENST00000529533.6	TSL:1 MANE Select	c.*1222_*1229dupGTGTGTGT		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+89_1447+96dupACACACAC		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1222_*1229dupGTGTGTGT		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes AF: 0.000444 AC: 64 AN: 144006 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000209

Gnomad ASJ AF: 0.00177

Gnomad EAS AF: 0.000414

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00676

Gnomad NFE AF: 0.000121

Gnomad OTH AF: 0.000508

GnomAD4 exome AF: 0.000145 AC: 75 AN: 517806 Hom.: 0 Cov.: 0 AF XY: 0.000153 AC XY: 43 AN XY: 281628

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000759 AC: 12 AN: 15800

American (AMR) AF: 0.000114 AC: 4 AN: 35002

Ashkenazi Jewish (ASJ) AF: 0.000333 AC: 5 AN: 15000

East Asian (EAS) AF: 0.000130 AC: 4 AN: 30702

South Asian (SAS) AF: 0.000268 AC: 14 AN: 52154

European-Finnish (FIN) AF: 0.0000543 AC: 2 AN: 36856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1942

European-Non Finnish (NFE) AF: 0.000105 AC: 32 AN: 303604

Other (OTH) AF: 0.0000748 AC: 2 AN: 26746

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000111022), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000444 AC: 64 AN: 144102 Hom.: 0 Cov.: 0 AF XY: 0.000500 AC XY: 35 AN XY: 69946

African (AFR) AF: 0.00109 AC: 42 AN: 38480

American (AMR) AF: 0.000209 AC: 3 AN: 14380

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 6 AN: 3382

East Asian (EAS) AF: 0.000415 AC: 2 AN: 4816

South Asian (SAS) AF: 0.00 AC: 0 AN: 4424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9538

Middle Eastern (MID) AF: 0.00730 AC: 2 AN: 274

European-Non Finnish (NFE) AF: 0.000121 AC: 8 AN: 65934

Other (OTH) AF: 0.000503 AC: 1 AN: 1988

Alfa AF: 0.00 Hom.: 143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71047866; hg19: chr11-26581382;