rs7068246

Positions:

• chr10-28175824-G-A
• chr10-28175824-G-C
• chr10-28175824-G-T

Variant summary

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

The NM_001318170.2(MPP7):​c.157-25765C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,884 control chromosomes in the GnomAD database, including 7,816 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 0.29 (7816 hom., cov: 31)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

Genes affected

MPP7 (HGNC:26542): (MAGUK p55 scaffold protein 7) The protein encoded by this gene is a member of the p55 Stardust family of membrane-associated guanylate kinase (MAGUK) proteins, which function in the establishment of epithelial cell polarity. This family member forms a complex with the polarity protein DLG1 (discs, large homolog 1) and facilitates epithelial cell polarity and tight junction formation. Polymorphisms in this gene are associated with variations in site-specific bone mineral density (BMD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.157-25765C>T		intron_variant		ENST00000683449.1	NP_001305099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000683449.1	c.157-25765C>T		intron_variant			NM_001318170.2	ENSP00000507917	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44448 AN: 151766 Hom.: 7794 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.293 AC: 44510 AN: 151884 Hom.: 7816 Cov.: 31 AF XY: 0.292 AC XY: 21664 AN XY: 74224

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.276

Alfa AF: 0.186 Hom.: 1370

Bravo AF: 0.315

Asia WGS AF: 0.350 AC: 1218 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs7068246; hg19: chr10-28464753;