rs11283943

chr5-113071088-G-GCCTCGCACTGTCTTchr5-113071088-G-GCCTCGCGCGGTCTTchr5-113071088-G-GCCTCGCGCTGTCTTchr5-113071088-G-GCCTCGTGCTGTCTTchr5-113071088-G-GCCTCTCGCTGTCTTchr5-113071088-G-GCCTTGCGCTGTCTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001085377.2(MCC):c.1925+5_1925+6insAAGACAGTGCGAGG variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,610,664 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: MCC NM_001085377.2 splice_donor_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCC	NM_001085377.2	c.1925+5_1925+6insAAGACAGTGCGAGG		splice_donor_region_variant, intron_variant		ENST00000408903.7
MCC	NM_002387.3	c.1355+5_1355+6insAAGACAGTGCGAGG		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCC	ENST00000408903.7	c.1925+5_1925+6insAAGACAGTGCGAGG		splice_donor_region_variant, intron_variant		2	NM_001085377.2	P1
MCC	ENST00000302475.9	c.1355+5_1355+6insAAGACAGTGCGAGG		splice_donor_region_variant, intron_variant		1
MCC	ENST00000514701.5	c.1355+5_1355+6insAAGACAGTGCGAGG		splice_donor_region_variant, intron_variant		2
MCC	ENST00000515367.6	c.1166+5_1166+6insAAGACAGTGCGAGG		splice_donor_region_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 151824 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000338 AC: 82 AN: 242414 Hom.: 0 AF XY: 0.000374 AC XY: 49 AN XY: 131162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00455

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000153 AC: 223 AN: 1458722 Hom.: 0 Cov.: 35 AF XY: 0.000160 AC XY: 116 AN XY: 725516

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00546

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000830

GnomAD4 genome AF: 0.000125 AC: 19 AN: 151942 Hom.: 0 Cov.: 0 AF XY: 0.000148 AC XY: 11 AN XY: 74242

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00368

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000398 Hom.: 1195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11283943; hg19: chr5-112406785;