rs151182874

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-113029018-C-A
• chr5-113029018-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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.2795G>T	p.Ser932Ile	missense_variant	Exon 18 of 19	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.2225G>T	p.Ser742Ile	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.2795G>T	p.Ser932Ile	missense_variant	Exon 18 of 19	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.2225G>T	p.Ser742Ile	missense_variant	Exon 16 of 17	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.2036G>T	p.Ser679Ile	missense_variant	Exon 16 of 17	5		ENSP00000421615.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.018	D;D;D
Sift4G	Benign	0.088	T;T;T
Polyphen		0.97	D;.;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

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: rs151182874; hg19: chr5-112364715;