rs1951936

Variant names:

• chr10-28104667-A-T
• rs1951936
• NM_001318170.2:c.953-14826T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318170.2(MPP7):​c.953-14826T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,104 control chromosomes in the GnomAD database, including 12,091 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 0.34 (12091 hom., cov: 32)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.953-14826T>A		intron_variant	Intron 11 of 16	ENST00000683449.1	NP_001305099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000683449.1	c.953-14826T>A		intron_variant	Intron 11 of 16		NM_001318170.2	ENSP00000507917.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51495 AN: 151986 Hom.: 12058 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.339 AC: 51589 AN: 152104 Hom.: 12091 Cov.: 32 AF XY: 0.349 AC XY: 25956 AN XY: 74358

African (AFR) AF: 0.549 AC: 22791 AN: 41478

American (AMR) AF: 0.419 AC: 6405 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3470

East Asian (EAS) AF: 0.947 AC: 4896 AN: 5168

South Asian (SAS) AF: 0.505 AC: 2436 AN: 4822

European-Finnish (FIN) AF: 0.265 AC: 2808 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11007 AN: 67984

Other (OTH) AF: 0.325 AC: 687 AN: 2114

Alfa AF: 0.258 Hom.: 896

Bravo AF: 0.365

Asia WGS AF: 0.740 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.044
DANN	Benign	0.42
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1951936; hg19: chr10-28393596;