rs3185733

Variant names:

• chr5-113023323-A-C
• rs3185733
• NM_001085377.2:c.*3979T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-113023323-A-C
• chr5-113023323-A-G
• chr5-113023323-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.*3979T>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.*3979T>G		3_prime_UTR_variant	Exon 17 of 17		NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.*3979T>G		3_prime_UTR_variant	Exon 19 of 19	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.*3979T>G		3_prime_UTR_variant	Exon 17 of 17	1		ENSP00000305617.4

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

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: 4 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.200 AC: 8302 AN: 41492

American (AMR) AF: 0.556 AC: 8503 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1871 AN: 3466

East Asian (EAS) AF: 0.629 AC: 3251 AN: 5168

South Asian (SAS) AF: 0.577 AC: 2783 AN: 4822

European-Finnish (FIN) AF: 0.461 AC: 4882 AN: 10584

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33379 AN: 67966

Other (OTH) AF: 0.472 AC: 996 AN: 2110

Alfa AF: 0.437 Hom.: 4419

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
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3185733; hg19: chr5-112359020;