5-113029030-T-C

Variant names:

• chr5-113029030-T-C
• NM_001085377.2:c.2783A>G

Variant summary

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

The NM_001085377.2(MCC):​c.2783A>G​(p.Gln928Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: MCC NM_001085377.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.2783A>G	p.Gln928Arg	missense_variant	Exon 18 of 19	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.2213A>G	p.Gln738Arg	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.2783A>G	p.Gln928Arg	missense_variant	Exon 18 of 19	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.2213A>G	p.Gln738Arg	missense_variant	Exon 16 of 17	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.2024A>G	p.Gln675Arg	missense_variant	Exon 16 of 17	5		ENSP00000421615.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2783A>G (p.Q928R) alteration is located in exon 18 (coding exon 18) of the MCC gene. This alteration results from a A to G substitution at nucleotide position 2783, causing the glutamine (Q) at amino acid position 928 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D;D;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.93	P;.;D
Vest4		0.82
MutPred		0.54		Gain of methylation at Q738 (P = 0.0236);.;.;
MVP		0.64
MPC		0.43
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.67
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-112364727;