NM_005961.3:c.4536_4537insT

Variant names:

• chr11-1018264-G-GA
• rs1856718594
• NM_005961.3:c.4536_4537insT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005961.3(MUC6):​c.4536_4537insT​(p.His1513SerfsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 1,535,956 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000029 (0 hom., cov: 56)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: MUC6 NM_005961.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -1.81

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC6	NM_005961.3	c.4536_4537insT	p.His1513SerfsTer24	frameshift_variant	Exon 31 of 33	ENST00000421673.7	NP_005952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC6	ENST00000421673.7	c.4536_4537insT	p.His1513SerfsTer24	frameshift_variant	Exon 31 of 33	5	NM_005961.3	ENSP00000406861.2

Frequencies

GnomAD3 genomes AF: 0.0000295 AC: 4 AN: 135598 Hom.: 0 Cov.: 56

Gnomad AFR AF: 0.0000270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000740

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000219

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1400258 Hom.: 0 Cov.: 150 AF XY: 0.00000574 AC XY: 4 AN XY: 697090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000487

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.41e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000295 AC: 4 AN: 135698 Hom.: 0 Cov.: 56 AF XY: 0.0000605 AC XY: 4 AN XY: 66100

Gnomad4 AFR AF: 0.0000269

Gnomad4 AMR AF: 0.0000739

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000220

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000108

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00180 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Lung cancer Pathogenic:1

Jun 15, 2021

Arun Kumar Laboratory, Indian Institute of Science

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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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: rs1856718594; hg19: chr11-1018264;