chr11-26559835-TACACACACACACAC-T

Variant names:

• chr11-26559835-TACACACACACACAC-T
• rs71047866
• NM_001135091.2:c.*1216_*1229delGTGTGTGTGTGTGT

Variant summary

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

The NM_001135091.2(MUC15):​c.*1216_*1229delGTGTGTGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 661,908 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00027 (1 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: 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.*1216_*1229delGTGTGTGTGTGTGT		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1447+83_1447+96delACACACACACACAC		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1216_*1229delGTGTGTGTGTGTGT		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.*1216_*1229delGTGTGTGTGTGTGT		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+83_1447+96delACACACACACACAC		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1216_*1229delGTGTGTGTGTGTGT		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 18 AN: 144006 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000167

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000274 AC: 142 AN: 517806 Hom.: 1 AF XY: 0.000263 AC XY: 74 AN XY: 281638

African (AFR) AF: 0.000127 AC: 2 AN: 15804

American (AMR) AF: 0.000114 AC: 4 AN: 35004

Ashkenazi Jewish (ASJ) AF: 0.0000667 AC: 1 AN: 15000

East Asian (EAS) AF: 0.0000326 AC: 1 AN: 30704

South Asian (SAS) AF: 0.000153 AC: 8 AN: 52160

European-Finnish (FIN) AF: 0.000163 AC: 6 AN: 36854

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

European-Non Finnish (NFE) AF: 0.000349 AC: 106 AN: 303592

Other (OTH) AF: 0.000523 AC: 14 AN: 26746

GnomAD4 genome AF: 0.000125 AC: 18 AN: 144102 Hom.: 0 Cov.: 0 AF XY: 0.0000715 AC XY: 5 AN XY: 69946

African (AFR) AF: 0.000182 AC: 7 AN: 38482

American (AMR) AF: 0.00 AC: 0 AN: 14380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4816

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.000167 AC: 11 AN: 65934

Other (OTH) AF: 0.00 AC: 0 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		0.70

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;