NM_001135091.2:c.*1228_*1229delGT

Variant names:

• chr11-26559835-TAC-T
• rs71047866
• NM_001135091.2:c.*1228_*1229delGT

Variant summary

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

The NM_001135091.2(MUC15):​c.*1228_*1229delGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 650,062 control chromosomes in the GnomAD database, including 2,427 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2166 hom., cov: 0)
  • Exomes 𝑓: 0.15 (261 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, G2P, Orphanet

ACMG classification

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

• BP6: Variant 11-26559835-TAC-T is Benign according to our data. Variant chr11-26559835-TAC-T is described in ClinVar as Benign. ClinVar VariationId is 1238462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 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.*1228_*1229delGT		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1447+95_1447+96delAC		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1228_*1229delGT		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.*1228_*1229delGT		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+95_1447+96delAC		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1228_*1229delGT		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes AF: 0.179 AC: 25690 AN: 143732 Hom.: 2167 Cov.: 0

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0962

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.152 AC: 76751 AN: 506240 Hom.: 261 AF XY: 0.150 AC XY: 41186 AN XY: 275272

African (AFR) AF: 0.147 AC: 2219 AN: 15092

American (AMR) AF: 0.181 AC: 6208 AN: 34318

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 2047 AN: 14678

East Asian (EAS) AF: 0.196 AC: 5871 AN: 29918

South Asian (SAS) AF: 0.110 AC: 5601 AN: 51090

European-Finnish (FIN) AF: 0.160 AC: 5779 AN: 36106

Middle Eastern (MID) AF: 0.154 AC: 292 AN: 1896

European-Non Finnish (NFE) AF: 0.150 AC: 44646 AN: 297088

Other (OTH) AF: 0.157 AC: 4088 AN: 26054

GnomAD4 genome AF: 0.179 AC: 25686 AN: 143822 Hom.: 2166 Cov.: 0 AF XY: 0.175 AC XY: 12180 AN XY: 69790

African (AFR) AF: 0.174 AC: 6676 AN: 38386

American (AMR) AF: 0.197 AC: 2824 AN: 14366

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 564 AN: 3378

East Asian (EAS) AF: 0.129 AC: 618 AN: 4806

South Asian (SAS) AF: 0.129 AC: 572 AN: 4422

European-Finnish (FIN) AF: 0.144 AC: 1370 AN: 9502

Middle Eastern (MID) AF: 0.173 AC: 47 AN: 272

European-Non Finnish (NFE) AF: 0.191 AC: 12559 AN: 65820

Other (OTH) AF: 0.187 AC: 371 AN: 1986

Alfa AF: 0.127 Hom.: 143

ClinVar

ClinVar submissions

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

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;