chr11-1017463-TTCTGGTGCCTGTACTGGTGTGGTTGGGGGTGATGCTGGTGGTAGAAGTTGAGGTGACTTCAGGATGGTGTGTGGAGGAAGTGTGTGAATGTAGGGATGTAGAGGTTTTGGCCGTGCTAAATGAGCTTCGGGATTGGCTG-T

Position:

• chr11-1017463-TTCTGGTGCCTGTACTGGTGTGGTTGGGGGTGATGCTGGTGGTAGAAGTTGAGGTGACTTCAGGATGGTGTGTGGAGGAAGTGTGTGAATGTAGGGATGTAGAGGTTTTGGCCGTGCTAAATGAGCTTCGGGATTGGCTG-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 8P and 1B. PVS1 BP6

The NM_005961.3(MUC6):​c.5199_5337del​(p.Ser1734ProfsTer69) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,405,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Likely benign (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 118)
  • Exomes 𝑓: 0.00018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.0270

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 Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BP6: Variant 11-1017463-TTCTGGTGCCTGTACTGGTGTGGTTGGGGGTGATGCTGGTGGTAGAAGTTGAGGTGACTTCAGGATGGTGTGTGGAGGAAGTGTGTGAATGTAGGGATGTAGAGGTTTTGGCCGTGCTAAATGAGCTTCGGGATTGGCTG-T is Benign according to our data. Variant chr11-1017463-TTCTGGTGCCTGTACTGGTGTGGTTGGGGGTGATGCTGGTGGTAGAAGTTGAGGTGACTTCAGGATGGTGTGTGGAGGAAGTGTGTGAATGTAGGGATGTAGAGGTTTTGGCCGTGCTAAATGAGCTTCGGGATTGGCTG-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC6	NM_005961.3	c.5199_5337del	p.Ser1734ProfsTer69	frameshift_variant	31/33	ENST00000421673.7	NP_005952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC6	ENST00000421673.7	c.5199_5337del	p.Ser1734ProfsTer69	frameshift_variant	31/33	5	NM_005961.3	ENSP00000406861	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 487 AN: 139470 Hom.: 0 Cov.: 118 FAILED QC

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00353

Gnomad AMR AF: 0.00422

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.00107

Gnomad SAS AF: 0.000447

Gnomad FIN AF: 0.00661

Gnomad MID AF: 0.00340

Gnomad NFE AF: 0.00365

Gnomad OTH AF: 0.00686

GnomAD4 exome AF: 0.000181 AC: 254 AN: 1405114 Hom.: 0 AF XY: 0.000189 AC XY: 132 AN XY: 698454

Gnomad4 AFR exome AF: 0.0000309

Gnomad4 AMR exome AF: 0.000167

Gnomad4 ASJ exome AF: 0.000164

Gnomad4 EAS exome AF: 0.000273

Gnomad4 SAS exome AF: 0.000193

Gnomad4 FIN exome AF: 0.00105

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.000245

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00352 AC: 491 AN: 139592 Hom.: 0 Cov.: 118 AF XY: 0.00360 AC XY: 247 AN XY: 68532

Gnomad4 AFR AF: 0.00271

Gnomad4 AMR AF: 0.00422

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.00107

Gnomad4 SAS AF: 0.000447

Gnomad4 FIN AF: 0.00661

Gnomad4 NFE AF: 0.00365

Gnomad4 OTH AF: 0.00836

Alfa AF: 0.0659 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Lung cancer Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1856666641; hg19: chr11-1017463;