11-26559835-TACACACAC-T

Position:

• chr11-26559835-TACACACAC-T

Variant summary

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

The NM_001135091.2(MUC15):​c.*1222_*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 0.109 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

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-TACACACAC-T is Benign according to our data. Variant chr11-26559835-TACACACAC-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.*1222_*1229del		3_prime_UTR_variant	5/5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+89_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.*1222_*1229del		3_prime_UTR_variant	5/5	1	NM_001135091.2	ENSP00000431983
ANO3	ENST00000256737.8	c.1447+89_1447+96del		intron_variant		1	NM_031418.4	ENSP00000256737	P3

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

Gnomad4 AFR exome AF: 0.0811

Gnomad4 AMR exome AF: 0.0620

Gnomad4 ASJ exome AF: 0.0914

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.0754

Gnomad4 FIN exome AF: 0.0873

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.112

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

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.0826

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.118

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

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;