chr11-26559835-T-TACAC

Position:

• chr11-26559835-T-TACAC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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

• Frequency:
  • Genomes: 𝑓 0.012 (11 hom., cov: 0)
  • Exomes 𝑓: 0.0067 (0 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-26559835-T-TACAC is Benign according to our data. Variant chr11-26559835-T-TACAC is described in ClinVar as [Likely_benign]. Clinvar id is 1195324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.*1229_*1230insGTGT		3_prime_UTR_variant	5/5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+93_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_*1230insGTGT		3_prime_UTR_variant	5/5	1	NM_001135091.2	ENSP00000431983
ANO3	ENST00000256737.8	c.1447+93_1447+96dup		intron_variant		1	NM_031418.4	ENSP00000256737	P3

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1688 AN: 143980 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.00693

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00766

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.00761

GnomAD4 exome AF: 0.00672 AC: 3471 AN: 516308 Hom.: 0 Cov.: 0 AF XY: 0.00682 AC XY: 1916 AN XY: 280814

Gnomad4 AFR exome AF: 0.00413

Gnomad4 AMR exome AF: 0.00604

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.00703

Gnomad4 SAS exome AF: 0.00696

Gnomad4 FIN exome AF: 0.0111

Gnomad4 NFE exome AF: 0.00615

Gnomad4 OTH exome AF: 0.00698

GnomAD4 genome AF: 0.0117 AC: 1689 AN: 144076 Hom.: 11 Cov.: 0 AF XY: 0.0124 AC XY: 868 AN XY: 69934

Gnomad4 AFR AF: 0.00694

Gnomad4 AMR AF: 0.00974

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00768

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0137

Gnomad4 OTH AF: 0.00755

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2020

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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;