rs10519336

Positions:

• chr5-113144407-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001085377.2(MCC):​c.742-1047C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,118 control chromosomes in the GnomAD database, including 6,458 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6458 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCC	NM_001085377.2	c.742-1047C>T		intron_variant		ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.172-1047C>T		intron_variant			NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.742-1047C>T		intron_variant		2	NM_001085377.2	ENSP00000386227	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43176 AN: 152000 Hom.: 6461 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.284 AC: 43189 AN: 152118 Hom.: 6458 Cov.: 32 AF XY: 0.285 AC XY: 21231 AN XY: 74376

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.261

Alfa AF: 0.272 Hom.: 2673

Bravo AF: 0.278

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10519336; hg19: chr5-112480104; COSMIC: COSV56726149;