11-26559835-TACACACACACACACACACACACACACAC-TACACACACACACACACACACACAC

Variant names:

• chr11-26559835-TACAC-T
• rs71047866
• NM_001135091.2:c.*1226_*1229delGTGT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001135091.2(MUC15):​c.*1226_*1229delGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 649,686 control chromosomes in the GnomAD database, including 2,231 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1760 hom., cov: 0)
  • Exomes 𝑓: 0.16 (471 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.701
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-26559835-TACAC-T is Benign according to our data. Variant chr11-26559835-TACAC-T is described in ClinVar as Benign. ClinVar VariationId is 1243722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

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.*1226_*1229delGTGT		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1447+93_1447+96delACAC		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1226_*1229delGTGT		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.*1226_*1229delGTGT		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+93_1447+96delACAC		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1226_*1229delGTGT		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes AF: 0.153 AC: 21978 AN: 143802 Hom.: 1762 Cov.: 0

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.157 AC: 79232 AN: 505788 Hom.: 471 AF XY: 0.158 AC XY: 43387 AN XY: 274890

African (AFR) AF: 0.0945 AC: 1452 AN: 15366

American (AMR) AF: 0.126 AC: 4314 AN: 34350

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 1926 AN: 14668

East Asian (EAS) AF: 0.165 AC: 4942 AN: 29914

South Asian (SAS) AF: 0.143 AC: 7285 AN: 50816

European-Finnish (FIN) AF: 0.159 AC: 5766 AN: 36200

Middle Eastern (MID) AF: 0.145 AC: 277 AN: 1910

European-Non Finnish (NFE) AF: 0.166 AC: 49119 AN: 296452

Other (OTH) AF: 0.159 AC: 4151 AN: 26112

GnomAD4 genome AF: 0.153 AC: 21997 AN: 143898 Hom.: 1760 Cov.: 0 AF XY: 0.153 AC XY: 10670 AN XY: 69840

African (AFR) AF: 0.0911 AC: 3502 AN: 38434

American (AMR) AF: 0.140 AC: 2006 AN: 14358

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 458 AN: 3380

East Asian (EAS) AF: 0.158 AC: 757 AN: 4804

South Asian (SAS) AF: 0.206 AC: 910 AN: 4420

European-Finnish (FIN) AF: 0.162 AC: 1539 AN: 9506

Middle Eastern (MID) AF: 0.184 AC: 50 AN: 272

European-Non Finnish (NFE) AF: 0.186 AC: 12239 AN: 65854

Other (OTH) AF: 0.171 AC: 339 AN: 1986

Alfa AF: 0.140 Hom.: 143

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonia 24 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs71047866; hg19: chr11-26581382; COSMIC: COSV55552561; COSMIC: COSV55552561;