rs3905706

chr10-28191013-C-T

Variant summary

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

The NM_001318170.2(MPP7):c.156+11140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,878 control chromosomes in the GnomAD database, including 10,252 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 0.32 (10252 hom., cov: 32)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPP7	NM_001318170.2	c.156+11140G>A		intron_variant		ENST00000683449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPP7	ENST00000683449.1	c.156+11140G>A		intron_variant			NM_001318170.2	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49168 AN: 151760 Hom.: 10231 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.324 AC: 49236 AN: 151878 Hom.: 10252 Cov.: 32 AF XY: 0.321 AC XY: 23804 AN XY: 74194

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.295

Alfa AF: 0.234 Hom.: 2371

Bravo AF: 0.354

Asia WGS AF: 0.304 AC: 1058 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.4
Dann	Benign	0.83

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: rs3905706; hg19: chr10-28479942;