rs7928987

Variant names:

• chr11-26559977-C-T
• rs7928987
• NM_001135091.2:c.*1088G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001135091.2(MUC15):​c.*1088G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 440,510 control chromosomes in the GnomAD database, including 1,874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1028 hom., cov: 32)
  • Exomes 𝑓: 0.071 (846 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.120
• Publications: 4 publications found

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]

ANO3 Gene-Disease associations (from GenCC):

• dystonia 24

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-26559977-C-T is Benign according to our data. Variant chr11-26559977-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135091.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC15	NM_001135091.2	MANE Select	c.*1088G>A		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1447+198C>T		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1088G>A		3_prime_UTR	Exon 4 of 4	NP_663625.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC15	ENST00000529533.6	TSL:1 MANE Select	c.*1088G>A		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+198C>T		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1088G>A		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15280 AN: 151848 Hom.: 1021 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0892

Gnomad EAS AF: 0.0381

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0921

GnomAD4 exome AF: 0.0707 AC: 20409 AN: 288544 Hom.: 846 Cov.: 4 AF XY: 0.0720 AC XY: 10778 AN XY: 149698

African (AFR) AF: 0.173 AC: 1528 AN: 8814

American (AMR) AF: 0.0529 AC: 602 AN: 11380

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 894 AN: 9978

East Asian (EAS) AF: 0.0244 AC: 629 AN: 25784

South Asian (SAS) AF: 0.117 AC: 1318 AN: 11226

European-Finnish (FIN) AF: 0.0453 AC: 1046 AN: 23114

Middle Eastern (MID) AF: 0.0783 AC: 106 AN: 1354

European-Non Finnish (NFE) AF: 0.0721 AC: 12901 AN: 179008

Other (OTH) AF: 0.0774 AC: 1385 AN: 17886

GnomAD4 genome AF: 0.101 AC: 15317 AN: 151966 Hom.: 1028 Cov.: 32 AF XY: 0.100 AC XY: 7432 AN XY: 74292

African (AFR) AF: 0.180 AC: 7458 AN: 41464

American (AMR) AF: 0.0630 AC: 958 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0892 AC: 309 AN: 3464

East Asian (EAS) AF: 0.0381 AC: 197 AN: 5164

South Asian (SAS) AF: 0.133 AC: 639 AN: 4816

European-Finnish (FIN) AF: 0.0383 AC: 406 AN: 10592

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0734 AC: 4984 AN: 67948

Other (OTH) AF: 0.0988 AC: 208 AN: 2106

Alfa AF: 0.106 Hom.: 203

Bravo AF: 0.104

Asia WGS AF: 0.108 AC: 374 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.71
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7928987; hg19: chr11-26581524;