chr5-113448310-G-T

Variant names:

• chr5-113448310-G-T
• rs10053341
• NM_001085377.2:c.170+39935C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085377.2(MCC):​c.170+39935C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,158 control chromosomes in the GnomAD database, including 2,102 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 0.16 (2101 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 0 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]

LOC107986366 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085377.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCC	NM_001085377.2	MANE Select	c.170+39935C>A		intron	N/A	NP_001078846.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCC	ENST00000408903.7	TSL:2 MANE Select	c.170+39935C>A		intron	N/A	ENSP00000386227.3
	MCC	ENST00000511242.1	TSL:3	n.580-23C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24239 AN: 152038 Hom.: 2099 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.159 AC: 24249 AN: 152156 Hom.: 2101 Cov.: 32 AF XY: 0.155 AC XY: 11564 AN XY: 74372

African (AFR) AF: 0.116 AC: 4803 AN: 41542

American (AMR) AF: 0.123 AC: 1882 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.0893 AC: 462 AN: 5172

South Asian (SAS) AF: 0.125 AC: 601 AN: 4814

European-Finnish (FIN) AF: 0.159 AC: 1685 AN: 10584

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13728 AN: 67972

Other (OTH) AF: 0.149 AC: 316 AN: 2114

Alfa AF: 0.0630 Hom.: 57

Bravo AF: 0.155

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.67
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10053341; hg19: chr5-112784007;