5-113245556-G-C

Variant names:

• chr5-113245556-G-C
• rs10519342
• NM_001085377.2:c.628-94134C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085377.2(MCC):​c.628-94134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 151,918 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.035 (252 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.628-94134C>G		intron_variant	Intron 3 of 18	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.57+48773C>G		intron_variant	Intron 1 of 16		NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.628-94134C>G		intron_variant	Intron 3 of 18	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.57+48773C>G		intron_variant	Intron 1 of 16	1		ENSP00000305617.4
MCC	ENST00000514701.5	c.57+48773C>G		intron_variant	Intron 1 of 13	2		ENSP00000485220.1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5301 AN: 151800 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00586

Gnomad OTH AF: 0.0331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0349 AC: 5306 AN: 151918 Hom.: 252 Cov.: 32 AF XY: 0.0340 AC XY: 2521 AN XY: 74254

African (AFR) AF: 0.107 AC: 4437 AN: 41398

American (AMR) AF: 0.0164 AC: 250 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3464

East Asian (EAS) AF: 0.00484 AC: 25 AN: 5166

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4814

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10540

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00586 AC: 398 AN: 67958

Other (OTH) AF: 0.0328 AC: 69 AN: 2106

Alfa AF: 0.000444 Hom.: 0

Bravo AF: 0.0410

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.65
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs10519342; hg19: chr5-112581253;