10-28094004-A-C

Position:

• chr10-28094004-A-C

Variant summary

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

The NM_001318170.2(MPP7):​c.953-4163T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,094 control chromosomes in the GnomAD database, including 20,174 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 0.47 (20174 hom., cov: 32)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

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 (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.953-4163T>G		intron_variant		ENST00000683449.1	NP_001305099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000683449.1	c.953-4163T>G		intron_variant			NM_001318170.2	ENSP00000507917	P1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71167 AN: 151976 Hom.: 20176 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.468 AC: 71153 AN: 152094 Hom.: 20174 Cov.: 32 AF XY: 0.462 AC XY: 34327 AN XY: 74362

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.492

Alfa AF: 0.600 Hom.: 43307

Bravo AF: 0.440

Asia WGS AF: 0.161 AC: 561 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	1.1
DANN	Benign	0.52

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: rs927675; hg19: chr10-28382933;