MUC1 p.Thr22Thr

Variant names:

• chr1-155192302-C-C
• ENST00000368392.7:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-155192303--
• chr1-155192303-T-A
• chr1-155192303-T-G
• chr1-155192303-T-C

Variant summary

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

The NM_001204288.2(MUC1):​c. variant causes a exon region 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MUC1 NM_001204288.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 0 publications found

Genes affected

MUC1 (HGNC:7508): (mucin 1, cell surface associated) This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]

MUC1 Gene-Disease associations (from GenCC):

• tubulointerstitial kidney disease, autosomal dominant, 2

  Inheritance: Unknown, AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen

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_001204288.2. 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
	MUC1	NM_001371720.2		c.		exon_region	Exon 2 of 12	NP_001358649.2
	MUC1	NM_001204286.1		c.		exon_region	Exon 2 of 8	NP_001191215.1	P15941
	MUC1	NM_001204287.2		c.		exon_region	Exon 2 of 8	NP_001191216.1	A5YRU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC1	ENST00000368392.7	TSL:1	c.		exon_region	Exon 2 of 8	ENSP00000357377.3	P15941-11
	MUC1	ENST00000338684.9	TSL:1	c.		exon_region	Exon 2 of 7	ENSP00000343482.6	A0A0A0MRB3
	MUC1	ENST00000610359.4	TSL:1	c.		exon_region	Exon 2 of 7	ENSP00000483482.1	A0A087X0L2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-155162093;