11-26559835-TACACACACACACACACAC-TACACAC

Variant names:

• chr11-26559835-TACACACACACAC-T
• rs71047866
• NM_001135091.2:c.*1218_*1229delGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001135091.2(MUC15):​c.*1218_*1229delGTGTGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 661,392 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.*1218_*1229delGTGTGTGTGTGT		3_prime_UTR_variant	Exon 5 of 5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+85_1447+96delACACACACACAC		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.*1218_*1229delGTGTGTGTGTGT		3_prime_UTR_variant	Exon 5 of 5	1	NM_001135091.2	ENSP00000431983.1
ANO3	ENST00000256737.8	c.1447+85_1447+96delACACACACACAC		intron_variant	Intron 14 of 26	1	NM_031418.4	ENSP00000256737.3

Frequencies

GnomAD3 genomes AF: 0.000743 AC: 107 AN: 144010 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000557

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000207

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000734

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00117

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00185 AC: 957 AN: 517286 Hom.: 0 AF XY: 0.00178 AC XY: 501 AN XY: 281348

Gnomad4 AFR exome AF: 0.00209

Gnomad4 AMR exome AF: 0.000657

Gnomad4 ASJ exome AF: 0.00294

Gnomad4 EAS exome AF: 0.00117

Gnomad4 SAS exome AF: 0.000844

Gnomad4 FIN exome AF: 0.00109

Gnomad4 NFE exome AF: 0.00221

Gnomad4 OTH exome AF: 0.00243

GnomAD4 genome AF: 0.000743 AC: 107 AN: 144106 Hom.: 0 Cov.: 0 AF XY: 0.000672 AC XY: 47 AN XY: 69948

Gnomad4 AFR AF: 0.000364

Gnomad4 AMR AF: 0.000556

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000208

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000734

Gnomad4 NFE AF: 0.00117

Gnomad4 OTH AF: 0.00

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;