11-26559835-TACACACAC-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001135091.2(MUC15):​c.*1222_*1229delGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 658,634 control chromosomes in the GnomAD database, including 1,479 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1035 hom., cov: 0)
  • Exomes 𝑓: 0.11 (444 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-26559835-TACACACAC-T is Benign according to our data. Variant chr11-26559835-TACACACAC-T is described in ClinVar as Benign. ClinVar VariationId is 1235324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 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.*1222_*1229delGTGTGTGT		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1447+89_1447+96delACACACAC		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1222_*1229delGTGTGTGT		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_*1229delGTGTGTGT		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+89_1447+96delACACACAC		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1222_*1229delGTGTGTGT		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes AF: 0.121 AC: 17473 AN: 143918 Hom.: 1035 Cov.: 0

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.105 AC: 54210 AN: 514620 Hom.: 444 AF XY: 0.105 AC XY: 29446 AN XY: 279838

African (AFR) AF: 0.0811 AC: 1270 AN: 15666

American (AMR) AF: 0.0620 AC: 2162 AN: 34888

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 1364 AN: 14930

East Asian (EAS) AF: 0.117 AC: 3580 AN: 30564

South Asian (SAS) AF: 0.0754 AC: 3901 AN: 51766

European-Finnish (FIN) AF: 0.0873 AC: 3203 AN: 36700

Middle Eastern (MID) AF: 0.115 AC: 220 AN: 1918

European-Non Finnish (NFE) AF: 0.118 AC: 35540 AN: 301626

Other (OTH) AF: 0.112 AC: 2970 AN: 26562

GnomAD4 genome AF: 0.121 AC: 17476 AN: 144014 Hom.: 1035 Cov.: 0 AF XY: 0.119 AC XY: 8319 AN XY: 69904

African (AFR) AF: 0.105 AC: 4029 AN: 38452

American (AMR) AF: 0.115 AC: 1659 AN: 14372

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 369 AN: 3382

East Asian (EAS) AF: 0.140 AC: 675 AN: 4814

South Asian (SAS) AF: 0.0826 AC: 365 AN: 4420

European-Finnish (FIN) AF: 0.0916 AC: 873 AN: 9530

Middle Eastern (MID) AF: 0.153 AC: 42 AN: 274

European-Non Finnish (NFE) AF: 0.138 AC: 9101 AN: 65896

Other (OTH) AF: 0.118 AC: 235 AN: 1988

Alfa AF: 0.0861 Hom.: 143

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	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

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: COSV55553332; COSMIC: COSV55553332;