11-26559835-TACACACACACACACACAC-TACACACAC

Variant names:

• chr11-26559835-TACACACACAC-T
• rs71047866
• NM_001135091.2:c.*1220_*1229delGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001135091.2(MUC15):​c.*1220_*1229delGTGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 659,994 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0053 (4 hom., cov: 0)
  • Exomes 𝑓: 0.019 (4 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.019 (9818/515918) while in subpopulation EAS AF= 0.0251 (769/30598). AF 95% confidence interval is 0.0237. There are 4 homozygotes in gnomad4_exome. There are 5302 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• 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.*1220_*1229delGTGTGTGTGT		3_prime_UTR_variant	Exon 5 of 5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+87_1447+96delACACACACAC		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	ENST00000529533.6	c.*1220_*1229delGTGTGTGTGT		3_prime_UTR_variant	Exon 5 of 5	1	NM_001135091.2	ENSP00000431983.1
ANO3	ENST00000256737.8	c.1447+87_1447+96delACACACACAC		intron_variant	Intron 14 of 26	1	NM_031418.4	ENSP00000256737.3

Frequencies

GnomAD3 genomes AF: 0.00527 AC: 759 AN: 143980 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00571

Gnomad ASJ AF: 0.0272

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.000451

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000940

Gnomad OTH AF: 0.00457

GnomAD4 exome AF: 0.0190 AC: 9818 AN: 515918 Hom.: 4 AF XY: 0.0189 AC XY: 5302 AN XY: 280616

Gnomad4 AFR exome AF: 0.0227

Gnomad4 AMR exome AF: 0.0122

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.0251

Gnomad4 SAS exome AF: 0.0127

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.00527 AC: 759 AN: 144076 Hom.: 4 Cov.: 0 AF XY: 0.00566 AC XY: 396 AN XY: 69932

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.00577

Gnomad4 ASJ AF: 0.0272

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.000226

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000940

Gnomad4 OTH AF: 0.00453

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;