rs773046677

Variant names:

• chr5-113029027-T-A
• NM_001085377.2:c.2786A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-113029027-T-A
• chr5-113029027-T-C

Variant summary

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

The NM_001085377.2(MCC):​c.2786A>T​(p.Glu929Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,232 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: 0.0000014 (0 hom.)
• Consequence: MCC NM_001085377.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.39

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, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.2786A>T	p.Glu929Val	missense_variant	Exon 18 of 19	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.2216A>T	p.Glu739Val	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.2786A>T	p.Glu929Val	missense_variant	Exon 18 of 19	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.2216A>T	p.Glu739Val	missense_variant	Exon 16 of 17	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.2027A>T	p.Glu676Val	missense_variant	Exon 16 of 17	5		ENSP00000421615.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461232 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726918

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: 0.00000180

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	0.74
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.;.
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.021	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.86
MutPred		0.57		Loss of helix (P = 0.0444);.;.;
MVP		0.67
MPC		0.47
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.50
gMVP		0.42

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: chr5-112364724;