rs765973058

Variant names:

• chr7-100952650-AC-A
• rs765973058
• NM_005960.2:c.873delC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005960.2(MUC3A):​c.873delC​(p.Ile292PhefsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., cov: 43)
  • Failed GnomAD Quality Control
• Consequence: MUC3A NM_005960.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 3 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 2 ACMG points.

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

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.873delC	p.Ile292PhefsTer8	frameshift	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.873delC	p.Ile292PhefsTer8	frameshift	Exon 2 of 12	ENSP00000368771.5	Q02505-1
	MUC3A	ENST00000483366.5	TSL:5	c.873delC	p.Ile292PhefsTer8	frameshift	Exon 2 of 11	ENSP00000483541.1	Q02505-5
	MUC3A	ENST00000868577.1		c.61+2967delC		intron	N/A	ENSP00000538636.1

Frequencies

GnomAD3 genomes AF: 0.0000823 AC: 12 AN: 145852 Hom.: 0 Cov.: 43

Gnomad AFR AF: 0.0000758

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000691

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000438

Gnomad FIN AF: 0.0000983

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000458

Gnomad OTH AF: 0.000502

GnomAD4 exome Cov.: 79

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000822 AC: 12 AN: 145956 Hom.: 0 Cov.: 43 AF XY: 0.000112 AC XY: 8 AN XY: 71274

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

African (AFR) AF: 0.0000756 AC: 3 AN: 39690

American (AMR) AF: 0.0000690 AC: 1 AN: 14494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3348

East Asian (EAS) AF: 0.000199 AC: 1 AN: 5014

South Asian (SAS) AF: 0.000438 AC: 2 AN: 4562

European-Finnish (FIN) AF: 0.0000983 AC: 1 AN: 10178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000458 AC: 3 AN: 65490

Other (OTH) AF: 0.000497 AC: 1 AN: 2014

⚠️ 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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0

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

Other links and lift over

dbSNP: rs765973058; hg19: chr7-100550290;