11-26559835-TAC-T

Position:

• chr11-26559835-TAC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001135091.2(MUC15):​c.*1228_*1229del 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.*1228_*1229del		3_prime_UTR_variant	5/5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+95_1447+96del		intron_variant		ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC15	ENST00000529533.6	c.*1228_*1229del		3_prime_UTR_variant	5/5	1	NM_001135091.2	ENSP00000431983
ANO3	ENST00000256737.8	c.1447+95_1447+96del		intron_variant		1	NM_031418.4	ENSP00000256737	P3

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

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.157

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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.187

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs71047866; hg19: chr11-26581382;