11-26559835-TACACACACACACACACAC-TACACACACACACACACACACACAC

Variant names:

• chr11-26559835-T-TACACAC
• rs71047866
• NM_001135091.2:c.*1224_*1229dupGTGTGT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001135091.2(MUC15):​c.*1224_*1229dupGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0061 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.*1224_*1229dupGTGTGT		3_prime_UTR_variant	Exon 5 of 5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+91_1447+96dupACACAC		intron_variant	Intron 14 of 26	ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC15	ENST00000529533	c.*1224_*1229dupGTGTGT		3_prime_UTR_variant	Exon 5 of 5	1	NM_001135091.2	ENSP00000431983.1
ANO3	ENST00000256737.8	c.1447+91_1447+96dupACACAC		intron_variant	Intron 14 of 26	1	NM_031418.4	ENSP00000256737.3

Frequencies

GnomAD3 genomes AF: 0.00611 AC: 880 AN: 143980 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00745

Gnomad ASJ AF: 0.00532

Gnomad EAS AF: 0.00476

Gnomad SAS AF: 0.00451

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.00508

GnomAD4 exome AF: 0.00155 AC: 800 AN: 517586 Hom.: 0 Cov.: 0 AF XY: 0.00160 AC XY: 451 AN XY: 281498

Gnomad4 AFR exome AF: 0.00469

Gnomad4 AMR exome AF: 0.00146

Gnomad4 ASJ exome AF: 0.00127

Gnomad4 EAS exome AF: 0.00209

Gnomad4 SAS exome AF: 0.00203

Gnomad4 FIN exome AF: 0.00128

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.00180

GnomAD4 genome AF: 0.00612 AC: 882 AN: 144076 Hom.: 4 Cov.: 0 AF XY: 0.00585 AC XY: 409 AN XY: 69934

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.00744

Gnomad4 ASJ AF: 0.00532

Gnomad4 EAS AF: 0.00457

Gnomad4 SAS AF: 0.00452

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00294

Gnomad4 OTH AF: 0.00503

ClinVar

Not reported in ClinVar

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;