NM_001135091.2:c.*1364A>G

Variant names:

• chr11-26559701-T-C
• rs997547119
• NM_001135091.2:c.*1364A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001135091.2(MUC15):​c.*1364A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 1,442,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.361
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-26559701-T-C is Benign according to our data. Variant chr11-26559701-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1987682.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*1364A>G		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1387-18T>C		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1364A>G		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.*1364A>G		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1387-18T>C		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1364A>G		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251020 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000693 AC: 10 AN: 1442154 Hom.: 0 Cov.: 28 AF XY: 0.00000556 AC XY: 4 AN XY: 719014

African (AFR) AF: 0.00 AC: 0 AN: 33052

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39516

South Asian (SAS) AF: 0.00 AC: 0 AN: 85860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00000822 AC: 9 AN: 1094396

Other (OTH) AF: 0.00 AC: 0 AN: 59796

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.74
PhyloP100		0.36

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: rs997547119; hg19: chr11-26581248;