5-113023323-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001085377.2(MCC):​c.*3979T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,146 control chromosomes in the GnomAD database, including 51 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 0.023 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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=-0.94).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0229 (3478/152146) while in subpopulation AFR AF = 0.0325 (1348/41504). AF 95% confidence interval is 0.031. There are 51 homozygotes in GnomAd4. There are 1792 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.*3979T>C		3_prime_UTR_variant	Exon 19 of 19	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.*3979T>C		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>C		3_prime_UTR_variant	Exon 19 of 19	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.*3979T>C		3_prime_UTR_variant	Exon 17 of 17	1		ENSP00000305617.4

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3469 AN: 152028 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00828

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0182

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 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: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0229 AC: 3478 AN: 152146 Hom.: 51 Cov.: 32 AF XY: 0.0241 AC XY: 1792 AN XY: 74384

African (AFR) AF: 0.0325 AC: 1348 AN: 41504

American (AMR) AF: 0.00954 AC: 146 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4826

European-Finnish (FIN) AF: 0.0606 AC: 641 AN: 10584

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0181 AC: 1232 AN: 67984

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.00411 Hom.: 4419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.20
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism

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;