11-26559851-C-CAT

Position:

• chr11-26559851-C-CAT

Variant summary

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

The NM_001135091.2(MUC15):​c.*1213_*1214insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 863,900 control chromosomes in the GnomAD database, including 1,408 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (961 hom., cov: 29)
  • Exomes 𝑓: 0.054 (447 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

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 11-26559851-C-CAT is Benign according to our data. Variant chr11-26559851-C-CAT is described in ClinVar as [Benign]. Clinvar id is 1253720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.*1213_*1214insAT		3_prime_UTR_variant	5/5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+73_1447+74insTA		intron_variant		ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC15	ENST00000529533.6	c.*1213_*1214insAT		3_prime_UTR_variant	5/5	1	NM_001135091.2	ENSP00000431983
ANO3	ENST00000256737.8	c.1447+73_1447+74insTA		intron_variant		1	NM_031418.4	ENSP00000256737	P3

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14653 AN: 151292 Hom.: 956 Cov.: 29

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.0886

Gnomad EAS AF: 0.0330

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.0903

GnomAD4 exome AF: 0.0537 AC: 38232 AN: 712494 Hom.: 447 Cov.: 11 AF XY: 0.0559 AC XY: 21264 AN XY: 380140

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0387

Gnomad4 ASJ exome AF: 0.0686

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.0947

Gnomad4 FIN exome AF: 0.0327

Gnomad4 NFE exome AF: 0.0493

Gnomad4 OTH exome AF: 0.0603

GnomAD4 genome AF: 0.0970 AC: 14686 AN: 151406 Hom.: 961 Cov.: 29 AF XY: 0.0961 AC XY: 7110 AN XY: 74014

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.0886

Gnomad4 EAS AF: 0.0331

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0687

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.0208 Hom.: 12

Asia WGS AF: 0.0970 AC: 336 AN: 3478

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 21, 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: rs138818641; hg19: chr11-26581398;