7-100952867-CAGA-C

Variant names:

• chr7-100952867-CAGA-C
• rs1792004316
• NM_005960.2:c.1089_1091delAGA

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_Supporting BS1

The NM_005960.2(MUC3A):​c.1089_1091delAGA​(p.Glu364del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC3A NM_005960.2 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.336

Genes affected

MUC3A (HGNC:7513): (mucin 3A, cell surface associated) The mucin genes encode epithelial glycoproteins, some of which are secreted and some membrane bound. Each of the genes contains at least one large domain of tandemly repeated sequence that encodes the peptide sequence rich in serine and/or threonine residues, which carries most of the O-linked glycosylation (Gendler and Spicer, 1995 [PubMed 7778880]).[supplied by OMIM, Aug 2008]

LOC105375431 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005960.2. Strenght limited to Supporting due to length of the change: 1aa.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0325 (4744/145898) while in subpopulation AFR AF= 0.0459 (1819/39606). AF 95% confidence interval is 0.0442. There are 0 homozygotes in gnomad4. There are 2281 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC3A	NM_005960.2	c.1089_1091delAGA	p.Glu364del	disruptive_inframe_deletion	Exon 2 of 12	ENST00000379458.9	NP_005951.1
LOC105375431	XR_007060457.1	n.44-6119_44-6117delTCT		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC3A	ENST00000379458.9	c.1089_1091delAGA	p.Glu364del	disruptive_inframe_deletion	Exon 2 of 12	5	NM_005960.2	ENSP00000368771.5
MUC3A	ENST00000483366.5	c.1089_1091delAGA	p.Glu364del	disruptive_inframe_deletion	Exon 2 of 11	5		ENSP00000483541.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4741 AN: 145788 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.0403

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0286

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0199

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0198

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000414 AC: 537 AN: 1298328 Hom.: 0 AF XY: 0.000425 AC XY: 270 AN XY: 635608

Gnomad4 AFR exome AF: 0.000552

Gnomad4 AMR exome AF: 0.000596

Gnomad4 ASJ exome AF: 0.000716

Gnomad4 EAS exome AF: 0.000447

Gnomad4 SAS exome AF: 0.000671

Gnomad4 FIN exome AF: 0.000987

Gnomad4 NFE exome AF: 0.000356

Gnomad4 OTH exome AF: 0.000597

GnomAD4 genome AF: 0.0325 AC: 4744 AN: 145898 Hom.: 0 Cov.: 0 AF XY: 0.0320 AC XY: 2281 AN XY: 71358

Gnomad4 AFR AF: 0.0459

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.0286

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.0208

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.0206

Alfa AF: 0.00882 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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1792004316; hg19: chr7-100550507;