rs786399

Positions:

• chr10-28316597-A-G
• chr10-28316597-A-T

Variant summary

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

The ENST00000441595.2(MPP7):​c.-132+13332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,910 control chromosomes in the GnomAD database, including 11,580 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 0.37 (11580 hom., cov: 31)
• Consequence: MPP7 ENST00000441595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPP7	XM_047424647.1	c.-132+18273T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPP7	ENST00000441595.2	c.-132+13332T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56461 AN: 151792 Hom.: 11554 Cov.: 31

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.0703

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.372 AC: 56535 AN: 151910 Hom.: 11580 Cov.: 31 AF XY: 0.365 AC XY: 27112 AN XY: 74216

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.0704

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.340

Alfa AF: 0.335 Hom.: 17516

Bravo AF: 0.377

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs786399; hg19: chr10-28605526;