rs138818641

Variant names:

• chr11-26559851-C-CAT
• rs138818641
• NM_001135091.2:c.*1213_*1214insAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001135091.2(MUC15):​c.*1213_*1214insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 863,900 control chromosomes in the GnomAD database, including 1,408 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (961 hom., cov: 29)
  • Exomes 𝑓: 0.054 (447 hom.)
• Consequence: MUC15 NM_001135091.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• 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, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-26559851-C-CAT is Benign according to our data. Variant chr11-26559851-C-CAT is described in ClinVar as Benign. ClinVar VariationId is 1253720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 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.*1213_*1214insAT		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_031418.4	MANE Select	c.1447+73_1447+74insTA		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_145650.4		c.*1213_*1214insAT		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.*1213_*1214insAT		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+73_1447+74insTA		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000436318.6	TSL:5	c.*1213_*1214insAT		3_prime_UTR	Exon 4 of 4	ENSP00000416753.2	A0A0A0MT67

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14653 AN: 151292 Hom.: 956 Cov.: 29

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.0886

Gnomad EAS AF: 0.0330

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.0903

GnomAD4 exome AF: 0.0537 AC: 38232 AN: 712494 Hom.: 447 Cov.: 11 AF XY: 0.0559 AC XY: 21264 AN XY: 380140

African (AFR) AF: 0.137 AC: 2445 AN: 17888

American (AMR) AF: 0.0387 AC: 1524 AN: 39404

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 1342 AN: 19564

East Asian (EAS) AF: 0.0217 AC: 783 AN: 36018

South Asian (SAS) AF: 0.0947 AC: 6162 AN: 65062

European-Finnish (FIN) AF: 0.0327 AC: 1538 AN: 47014

Middle Eastern (MID) AF: 0.0641 AC: 163 AN: 2542

European-Non Finnish (NFE) AF: 0.0493 AC: 22164 AN: 449986

Other (OTH) AF: 0.0603 AC: 2111 AN: 35016

GnomAD4 genome AF: 0.0970 AC: 14686 AN: 151406 Hom.: 961 Cov.: 29 AF XY: 0.0961 AC XY: 7110 AN XY: 74014

African (AFR) AF: 0.177 AC: 7308 AN: 41262

American (AMR) AF: 0.0618 AC: 939 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.0886 AC: 307 AN: 3464

East Asian (EAS) AF: 0.0331 AC: 170 AN: 5140

South Asian (SAS) AF: 0.129 AC: 616 AN: 4784

European-Finnish (FIN) AF: 0.0322 AC: 340 AN: 10556

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0687 AC: 4651 AN: 67720

Other (OTH) AF: 0.0961 AC: 201 AN: 2092

Alfa AF: 0.0208 Hom.: 12

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs138818641; hg19: chr11-26581398; COSMIC: COSV55556241; COSMIC: COSV55556241;