11-26559835-TACACACACACACACACACACACACACAC-TACACACACACACACACACACACACACACACACAC

Variant names:

• chr11-26559835-T-TACACAC
• rs71047866
• NM_001135091.2:c.*1224_*1229dupGTGTGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001135091.2(MUC15):​c.*1224_*1229dupGTGTGT 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 0.0061 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.*1224_*1229dupGTGTGT		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1447+91_1447+96dupACACAC		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1224_*1229dupGTGTGT		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.*1224_*1229dupGTGTGT		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+91_1447+96dupACACAC		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1224_*1229dupGTGTGT		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes AF: 0.00611 AC: 880 AN: 143980 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00745

Gnomad ASJ AF: 0.00532

Gnomad EAS AF: 0.00476

Gnomad SAS AF: 0.00451

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.00508

GnomAD4 exome AF: 0.00155 AC: 800 AN: 517586 Hom.: 0 Cov.: 0 AF XY: 0.00160 AC XY: 451 AN XY: 281498

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

African (AFR) AF: 0.00469 AC: 74 AN: 15772

American (AMR) AF: 0.00146 AC: 51 AN: 34996

Ashkenazi Jewish (ASJ) AF: 0.00127 AC: 19 AN: 14990

East Asian (EAS) AF: 0.00209 AC: 64 AN: 30692

South Asian (SAS) AF: 0.00203 AC: 106 AN: 52130

European-Finnish (FIN) AF: 0.00128 AC: 47 AN: 36852

Middle Eastern (MID) AF: 0.00154 AC: 3 AN: 1942

European-Non Finnish (NFE) AF: 0.00128 AC: 388 AN: 303474

Other (OTH) AF: 0.00180 AC: 48 AN: 26738

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00612 AC: 882 AN: 144076 Hom.: 4 Cov.: 0 AF XY: 0.00585 AC XY: 409 AN XY: 69934

African (AFR) AF: 0.0126 AC: 483 AN: 38460

American (AMR) AF: 0.00744 AC: 107 AN: 14376

Ashkenazi Jewish (ASJ) AF: 0.00532 AC: 18 AN: 3382

East Asian (EAS) AF: 0.00457 AC: 22 AN: 4816

South Asian (SAS) AF: 0.00452 AC: 20 AN: 4424

European-Finnish (FIN) AF: 0.00283 AC: 27 AN: 9538

Middle Eastern (MID) AF: 0.00365 AC: 1 AN: 274

European-Non Finnish (NFE) AF: 0.00294 AC: 194 AN: 65932

Other (OTH) AF: 0.00503 AC: 10 AN: 1988

Alfa AF: 0.00252 Hom.: 143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism

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;