rs111749447

chr11-1018167-ATCG-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PM4_Supporting BP6_Moderate

The NM_005961.3(MUC6):c.4631_4633del(p.Thr1544del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,315,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0860

Genes affected

MUC6 (HGNC:7517): (mucin 6, oligomeric mucus/gel-forming) This gene encodes a member of the mucin protein family. Mucins are high molecular weight glycoproteins produced by many epithelial tissues. The protein encoded by this gene is secreted and forms an insoluble mucous barrier that protects the gut lumen. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Variant has high frequency in the AMR(1.2774E-4) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).
• PM4: Nonframeshift variant in NON repetitive region in NM_005961.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 11-1018167-ATCG-A is Benign according to our data. Variant chr11-1018167-ATCG-A is described in ClinVar as [Benign]. Clinvar id is 403202.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC6	NM_005961.3	c.4631_4633del	p.Thr1544del	inframe_deletion	31/33	ENST00000421673.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC6	ENST00000421673.7	c.4631_4633del	p.Thr1544del	inframe_deletion	31/33	5	NM_005961.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 20 AN: 105212 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.000273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000355

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000318

Gnomad SAS AF: 0.000346

Gnomad FIN AF: 0.000141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000992

Gnomad OTH AF: 0.000680

GnomAD4 exome AF: 0.00195 AC: 2565 AN: 1315560 Hom.: 0 AF XY: 0.00233 AC XY: 1528 AN XY: 655462

Gnomad4 AFR exome AF: 0.00295

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.00792

Gnomad4 EAS exome AF: 0.000262

Gnomad4 SAS exome AF: 0.00977

Gnomad4 FIN exome AF: 0.00222

Gnomad4 NFE exome AF: 0.000891

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000190 AC: 20 AN: 105260 Hom.: 0 Cov.: 33 AF XY: 0.000254 AC XY: 13 AN XY: 51142

Gnomad4 AFR AF: 0.000273

Gnomad4 AMR AF: 0.000354

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000319

Gnomad4 SAS AF: 0.000348

Gnomad4 FIN AF: 0.000141

Gnomad4 NFE AF: 0.0000992

Gnomad4 OTH AF: 0.000669

Alfa AF: 0.0301 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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: rs111749447; hg19: chr11-1018167;