chr11-26559835-T-TAC

Position:

• chr11-26559835-T-TAC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001135091.2(MUC15):​c.*1229_*1230insGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1958 hom., cov: 0)
  • Exomes 𝑓: 0.089 (33 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.333

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 -16 ACMG points.

• BP6: Variant 11-26559835-T-TAC is Benign according to our data. Variant chr11-26559835-T-TAC is described in ClinVar as [Benign]. Clinvar id is 1228643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.*1229_*1230insGT		3_prime_UTR_variant	5/5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+95_1447+96dup		intron_variant		ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC15	ENST00000529533.6	c.*1229_*1230insGT		3_prime_UTR_variant	5/5	1	NM_001135091.2	ENSP00000431983
ANO3	ENST00000256737.8	c.1447+95_1447+96dup		intron_variant		1	NM_031418.4	ENSP00000256737	P3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 23321 AN: 143784 Hom.: 1960 Cov.: 0

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.0889 AC: 45280 AN: 509604 Hom.: 33 Cov.: 0 AF XY: 0.0902 AC XY: 25001 AN XY: 277064

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.0827

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.0806

Gnomad4 SAS exome AF: 0.0989

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.0850

Gnomad4 OTH exome AF: 0.0892

GnomAD4 genome AF: 0.162 AC: 23315 AN: 143882 Hom.: 1958 Cov.: 0 AF XY: 0.166 AC XY: 11572 AN XY: 69834

Gnomad4 AFR AF: 0.0765

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.157

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Dystonia 24 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

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;