5-113028959-C-G

Variant names:

• chr5-113028959-C-G
• NM_001085377.2:c.2854G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001085377.2(MCC):​c.2854G>C​(p.Val952Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.2854G>C	p.Val952Leu	missense_variant	Exon 18 of 19	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.2284G>C	p.Val762Leu	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.2854G>C	p.Val952Leu	missense_variant	Exon 18 of 19	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.2284G>C	p.Val762Leu	missense_variant	Exon 16 of 17	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.2095G>C	p.Val699Leu	missense_variant	Exon 16 of 17	5		ENSP00000421615.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461730 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727176

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.041	D;D;T
Sift4G	Benign	0.065	T;T;T
Polyphen		0.97	D;.;D
Vest4		0.80
MutPred		0.48		Loss of MoRF binding (P = 0.0894);.;.;
MVP		0.54
MPC		0.43
ClinPred		0.85	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-112364656;