rs10519339

Variant names:

• chr5-113210780-G-A
• rs10519339
• NM_001085377.2:c.628-59358C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085377.2(MCC):​c.628-59358C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 152,210 control chromosomes in the GnomAD database, including 767 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 0.057 (767 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.628-59358C>T		intron_variant	Intron 3 of 18	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.58-59358C>T		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.628-59358C>T		intron_variant	Intron 3 of 18	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.58-59358C>T		intron_variant	Intron 1 of 16	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.-133+23657C>T		intron_variant	Intron 1 of 16	5		ENSP00000421615.2
MCC	ENST00000514701.5	c.58-59358C>T		intron_variant	Intron 1 of 13	2		ENSP00000485220.1

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8723 AN: 152094 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00588

Gnomad OTH AF: 0.0569

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

GnomAD4 genome AF: 0.0574 AC: 8742 AN: 152210 Hom.: 767 Cov.: 32 AF XY: 0.0558 AC XY: 4150 AN XY: 74416

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0252

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.00872

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00588

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0333 Hom.: 166

Bravo AF: 0.0661

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.73

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: rs10519339; hg19: chr5-112546477;