5-113071088-G-GCCTTGCGCTGTCTT

Position:

• chr5-113071088-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+6insAAGACAGCGCAAGG 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 0.000013 in 1,458,726 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: not found (cov: 0)
  • Exomes 𝑓: 0.000013 (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	Protein	UniProt
MCC	NM_001085377.2	c.1925+5_1925+6insAAGACAGCGCAAGG		splice_donor_region_variant, intron_variant		ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.1355+5_1355+6insAAGACAGCGCAAGG		splice_donor_region_variant, intron_variant			NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.1925+5_1925+6insAAGACAGCGCAAGG		splice_donor_region_variant, intron_variant		2	NM_001085377.2	ENSP00000386227	P1
MCC	ENST00000302475.9	c.1355+5_1355+6insAAGACAGCGCAAGG		splice_donor_region_variant, intron_variant		1		ENSP00000305617
MCC	ENST00000514701.5	c.1355+5_1355+6insAAGACAGCGCAAGG		splice_donor_region_variant, intron_variant		2		ENSP00000485220
MCC	ENST00000515367.6	c.1166+5_1166+6insAAGACAGCGCAAGG		splice_donor_region_variant, intron_variant		5		ENSP00000421615

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1458726 Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9 AN XY: 725518

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.0000498

GnomAD4 genome Cov.: 0

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;