chr11-26559977-C-T

Position:

• chr11-26559977-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000529533.6(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 ENST00000529533.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.120

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.*1088G>A		3_prime_UTR_variant	5/5	ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+198C>T		intron_variant		ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC15	ENST00000529533.6	c.*1088G>A		3_prime_UTR_variant	5/5	1	NM_001135091.2	ENSP00000431983
ANO3	ENST00000256737.8	c.1447+198C>T		intron_variant		1	NM_031418.4	ENSP00000256737	P3

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

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.0896

Gnomad4 EAS exome AF: 0.0244

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0453

Gnomad4 NFE exome AF: 0.0721

Gnomad4 OTH exome AF: 0.0774

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

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0630

Gnomad4 ASJ AF: 0.0892

Gnomad4 EAS AF: 0.0381

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.0988

Alfa AF: 0.104 Hom.: 190

Bravo AF: 0.104

Asia WGS AF: 0.108 AC: 374 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs7928987; hg19: chr11-26581524;