5-113071088-G-GCCTCTCGCTGTCTT

Variant names:

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

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+6insAAGACAGCGAGAGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,824 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 0.0000066 (0 hom., cov: 0)
• Consequence: MCC NM_001085377.2 splice_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 rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.1925+5_1925+6insAAGACAGCGAGAGG		splice_region_variant, intron_variant	Intron 12 of 18	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.1355+5_1355+6insAAGACAGCGAGAGG		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+6insAAGACAGCGAGAGG		splice_region_variant, intron_variant	Intron 12 of 18	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.1355+5_1355+6insAAGACAGCGAGAGG		splice_region_variant, intron_variant	Intron 10 of 16	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.1166+5_1166+6insAAGACAGCGAGAGG		splice_region_variant, intron_variant	Intron 10 of 16	5		ENSP00000421615.2
MCC	ENST00000514701.5	c.1355+5_1355+6insAAGACAGCGAGAGG		splice_region_variant, intron_variant	Intron 10 of 13	2		ENSP00000485220.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151824 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome Cov.: 35

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151824 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74114

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;