5-113071088-G-GCCTCGCGCGGTCTT

Variant names:

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

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+6insAAGACCGCGCGAGG 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: 10 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.1925+5_1925+6insAAGACCGCGCGAGG		splice_region_variant, intron_variant	Intron 12 of 18	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.1355+5_1355+6insAAGACCGCGCGAGG		splice_region_variant, intron_variant	Intron 10 of 16		NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.1925+5_1925+6insAAGACCGCGCGAGG		splice_region_variant, intron_variant	Intron 12 of 18	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.1355+5_1355+6insAAGACCGCGCGAGG		splice_region_variant, intron_variant	Intron 10 of 16	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.1166+5_1166+6insAAGACCGCGCGAGG		splice_region_variant, intron_variant	Intron 10 of 16	5		ENSP00000421615.2
MCC	ENST00000514701.5	c.1355+5_1355+6insAAGACCGCGCGAGG		splice_region_variant, intron_variant	Intron 10 of 13	2		ENSP00000485220.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458726 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 1110376

Other (OTH) AF: 0.0000166 AC: 1 AN: 60260

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 1195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;