chr5-113029022-C-A

Variant names:

• chr5-113029022-C-A
• rs139210825
• NM_001085377.2:c.2791G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001085377.2(MCC):​c.2791G>T​(p.Val931Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,348 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MCC NM_001085377.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.30

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.2791G>T	p.Val931Leu	missense_variant	Exon 18 of 19	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.2221G>T	p.Val741Leu	missense_variant	Exon 16 of 17		NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.2791G>T	p.Val931Leu	missense_variant	Exon 18 of 19	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.2221G>T	p.Val741Leu	missense_variant	Exon 16 of 17	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.2032G>T	p.Val678Leu	missense_variant	Exon 16 of 17	5		ENSP00000421615.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461348 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.55	N;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.44	N;N;N
REVEL	Benign	0.29
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.92	P;.;D
Vest4		0.76
MutPred		0.47		Loss of MoRF binding (P = 0.0945);.;.;
MVP		0.49
MPC		0.42
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.14
gMVP		0.40

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: rs139210825; hg19: chr5-112364719;