NM_001085377.2:c.1925+5_1925+6insAAGACAGAGCGAGG

Variant names:

• chr5-113071088-G-GCCTCGCTCTGTCTT
• rs11283943
• NM_001085377.2:c.1925+5_1925+6insAAGACAGAGCGAGG

Variant summary

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

The NM_001085377.2(MCC):​c.1925+5_1925+6insAAGACAGAGCGAGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,726 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MCC NM_001085377.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

MCC (HGNC:6935): (MCC regulator of WNT signaling pathway) This gene is a candidate colorectal tumor suppressor gene that is thought to negatively regulate cell cycle progression. The orthologous gene in the mouse expresses a phosphoprotein associated with the plasma membrane and membrane organelles, and overexpression of the mouse protein inhibits entry into S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085377.2. 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
	MCC	NM_001085377.2	MANE Select	c.1925+5_1925+6insAAGACAGAGCGAGG		splice_region intron	N/A	NP_001078846.2	P23508-2
	MCC	NM_002387.3		c.1355+5_1355+6insAAGACAGAGCGAGG		splice_region intron	N/A	NP_002378.2	P23508-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCC	ENST00000408903.7	TSL:2 MANE Select	c.1925+5_1925+6insAAGACAGAGCGAGG		splice_region intron	N/A	ENSP00000386227.3	P23508-2
	MCC	ENST00000302475.9	TSL:1	c.1355+5_1355+6insAAGACAGAGCGAGG		splice_region intron	N/A	ENSP00000305617.4	P23508-1
	MCC	ENST00000515367.6	TSL:5	c.1166+5_1166+6insAAGACAGAGCGAGG		splice_region intron	N/A	ENSP00000421615.2	D6REY2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458726 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725518

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

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.00 AC: 0 AN: 85572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110376

Other (OTH) AF: 0.00 AC: 0 AN: 60260

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs11283943; hg19: chr5-112406785;