rs3185733

chr5-113023323-A-Cchr5-113023323-A-Gchr5-113023323-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085377.2(MCC):c.*3979T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,110 control chromosomes in the GnomAD database, including 15,288 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 0.42 (15286 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: MCC NM_001085377.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCC	NM_001085377.2	c.*3979T>G		3_prime_UTR_variant	19/19	ENST00000408903.7
MCC	NM_002387.3	c.*3979T>G		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCC	ENST00000408903.7	c.*3979T>G		3_prime_UTR_variant	19/19	2	NM_001085377.2	P1
MCC	ENST00000302475.9	c.*3979T>G		3_prime_UTR_variant	17/17	1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64447 AN: 151988 Hom.: 15278 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.424 AC: 64486 AN: 152106 Hom.: 15286 Cov.: 32 AF XY: 0.428 AC XY: 31852 AN XY: 74364

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.472

Alfa AF: 0.434 Hom.: 3909

Bravo AF: 0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.14
Dann	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3185733; hg19: chr5-112359020;