chr7-100952867-CAGA-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

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: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005960.2. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005960.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC3A	NM_005960.2	MANE Select	c.1089_1091delAGA	p.Glu364del	disruptive_inframe_deletion	Exon 2 of 12	NP_005951.1	Q02505-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC3A	ENST00000379458.9	TSL:5 MANE Select	c.1089_1091delAGA	p.Glu364del	disruptive_inframe_deletion	Exon 2 of 12	ENSP00000368771.5	Q02505-1
	MUC3A	ENST00000483366.5	TSL:5	c.1089_1091delAGA	p.Glu364del	disruptive_inframe_deletion	Exon 2 of 11	ENSP00000483541.1	Q02505-5
	MUC3A	ENST00000868577.1		c.61+3183_61+3185delAGA		intron	N/A	ENSP00000538636.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000552 AC: 16 AN: 29004

American (AMR) AF: 0.000596 AC: 18 AN: 30196

Ashkenazi Jewish (ASJ) AF: 0.000716 AC: 15 AN: 20962

East Asian (EAS) AF: 0.000447 AC: 15 AN: 33564

South Asian (SAS) AF: 0.000671 AC: 44 AN: 65578

European-Finnish (FIN) AF: 0.000987 AC: 30 AN: 30398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4872

European-Non Finnish (NFE) AF: 0.000356 AC: 367 AN: 1030110

Other (OTH) AF: 0.000597 AC: 32 AN: 53644

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0459 AC: 1819 AN: 39606

American (AMR) AF: 0.0211 AC: 310 AN: 14704

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 96 AN: 3356

East Asian (EAS) AF: 0.0322 AC: 160 AN: 4974

South Asian (SAS) AF: 0.0208 AC: 97 AN: 4654

European-Finnish (FIN) AF: 0.0340 AC: 345 AN: 10146

Middle Eastern (MID) AF: 0.0211 AC: 6 AN: 284

European-Non Finnish (NFE) AF: 0.0281 AC: 1834 AN: 65270

Other (OTH) AF: 0.0206 AC: 42 AN: 2036

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00882 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1792004316; hg19: chr7-100550507;