NM_001135091.2:c.*1214_*1229delGTGTGTGTGTGTGTGT

Variant names:

• chr11-26559835-TACACACACACACACAC-T
• rs71047866
• NM_001135091.2:c.*1214_*1229delGTGTGTGTGTGTGTGT

Variant summary

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

The NM_001135091.2(MUC15):​c.*1214_*1229delGTGTGTGTGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000695 in 661,846 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 0.000049 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000075 (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.*1214_*1229delGTGTGTGTGTGTGTGT		3_prime_UTR_variant	Exon 5 of 5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+81_1447+96delACACACACACACACAC		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.*1214_*1229delGTGTGTGTGTGTGTGT		3_prime_UTR_variant	Exon 5 of 5	1	NM_001135091.2	ENSP00000431983.1
ANO3	ENST00000256737.8	c.1447+81_1447+96delACACACACACACACAC		intron_variant	Intron 14 of 26	1	NM_031418.4	ENSP00000256737.3

Frequencies

GnomAD3 genomes AF: 0.0000486 AC: 7 AN: 144008 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000414

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000607

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000753 AC: 39 AN: 517838 Hom.: 0 AF XY: 0.0000746 AC XY: 21 AN XY: 281646

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000286

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000423

Gnomad4 SAS exome AF: 0.000115

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000560

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000486 AC: 7 AN: 144008 Hom.: 0 Cov.: 0 AF XY: 0.0000716 AC XY: 5 AN XY: 69830

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000414

Gnomad4 SAS AF: 0.000226

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000607

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;