5-113029018-C-A

Variant names:

• chr5-113029018-C-A
• rs151182874
• NM_001085377.2:c.2795G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001085377.2(MCC):​c.2795G>T​(p.Ser932Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S932N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MCC NM_001085377.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCC	NM_001085377.2	MANE Select	c.2795G>T	p.Ser932Ile	missense	Exon 18 of 19	NP_001078846.2	P23508-2
	MCC	NM_002387.3		c.2225G>T	p.Ser742Ile	missense	Exon 16 of 17	NP_002378.2	P23508-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCC	ENST00000408903.7	TSL:2 MANE Select	c.2795G>T	p.Ser932Ile	missense	Exon 18 of 19	ENSP00000386227.3	P23508-2
	MCC	ENST00000302475.9	TSL:1	c.2225G>T	p.Ser742Ile	missense	Exon 16 of 17	ENSP00000305617.4	P23508-1
	MCC	ENST00000515367.6	TSL:5	c.2036G>T	p.Ser679Ile	missense	Exon 16 of 17	ENSP00000421615.2	D6REY2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Uncertain	0.018	D
Sift4G	Benign	0.088	T
Polyphen		0.97	D
Vest4		0.63
MutPred		0.54		Loss of disorder (P = 0.015)
MVP		0.68
MPC		0.19
ClinPred		0.73	D
GERP RS		5.6
Varity_R		0.28
gMVP		0.38
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs151182874; hg19: chr5-112364715;