10-28116482-G-T

Variant names:

• chr10-28116482-G-T
• rs7916852
• NM_001318170.2:c.952+3169C>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.952+3169C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,954 control chromosomes in the GnomAD database, including 7,223 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 0.26 (7223 hom., cov: 32)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.952+3169C>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.952+3169C>A		intron_variant	Intron 11 of 16		NM_001318170.2	ENSP00000507917.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39399 AN: 151836 Hom.: 7218 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.260 AC: 39432 AN: 151954 Hom.: 7223 Cov.: 32 AF XY: 0.272 AC XY: 20166 AN XY: 74254

African (AFR) AF: 0.360 AC: 14937 AN: 41458

American (AMR) AF: 0.335 AC: 5109 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4548 AN: 5166

South Asian (SAS) AF: 0.450 AC: 2163 AN: 4812

European-Finnish (FIN) AF: 0.247 AC: 2609 AN: 10552

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9073 AN: 67920

Other (OTH) AF: 0.246 AC: 517 AN: 2100

Alfa AF: 0.158 Hom.: 1675

Bravo AF: 0.276

Asia WGS AF: 0.663 AC: 2296 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.26
PhyloP100		0.0070
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: rs7916852; hg19: chr10-28405411;