11-1017036-G-GCA

Position:

• chr11-1017036-G-GCA

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The NM_005961.3(MUC6):​c.5764_5765insTG​(p.Thr1922MetfsTer64) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.29 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: -1.41

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 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC6	NM_005961.3	c.5764_5765insTG	p.Thr1922MetfsTer64	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.5764_5765insTG	p.Thr1922MetfsTer64	frameshift_variant	31/33	5	NM_005961.3	ENSP00000406861	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 14583 AN: 50342 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.253

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000430 AC: 59 AN: 1371078 Hom.: 0 Cov.: 286 AF XY: 0.0000440 AC XY: 30 AN XY: 681592

Gnomad4 AFR exome AF: 0.0000320

Gnomad4 AMR exome AF: 0.0000966

Gnomad4 ASJ exome AF: 0.0000421

Gnomad4 EAS exome AF: 0.0000283

Gnomad4 SAS exome AF: 0.0000628

Gnomad4 FIN exome AF: 0.000424

Gnomad4 NFE exome AF: 0.0000256

Gnomad4 OTH exome AF: 0.0000181

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.290 AC: 14619 AN: 50420 Hom.: 0 Cov.: 0 AF XY: 0.288 AC XY: 7302 AN XY: 25320

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.259

Alfa AF: 0.329 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Small cell lung carcinoma Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

- -

Lung cancer Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

- -

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: rs778367820; hg19: chr11-1017036;