10-28191013-C-T

Variant names:

• chr10-28191013-C-T
• rs3905706
• NM_001318170.2:c.156+11140G>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.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
• Publications: 28 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318170.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	NM_001318170.2	MANE Select	c.156+11140G>A		intron	N/A	NP_001305099.1	Q5T2T1-1
	MPP7	NM_173496.5		c.156+11140G>A		intron	N/A	NP_775767.2	Q5T2T1-1
	MPP7	NR_134517.2		n.491+11140G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	ENST00000683449.1	MANE Select	c.156+11140G>A		intron	N/A	ENSP00000507917.1	Q5T2T1-1
	MPP7	ENST00000375719.7	TSL:1	c.156+11140G>A		intron	N/A	ENSP00000364871.3	Q5T2T1-1
	MPP7	ENST00000496637.6	TSL:1	n.156+11140G>A		intron	N/A	ENSP00000473899.1	S4R337

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

African (AFR) AF: 0.573 AC: 23728 AN: 41422

American (AMR) AF: 0.369 AC: 5627 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3466

East Asian (EAS) AF: 0.432 AC: 2225 AN: 5152

South Asian (SAS) AF: 0.186 AC: 895 AN: 4816

European-Finnish (FIN) AF: 0.198 AC: 2084 AN: 10514

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.196 AC: 13286 AN: 67940

Other (OTH) AF: 0.295 AC: 622 AN: 2106

Alfa AF: 0.251 Hom.: 15290

Bravo AF: 0.354

Asia WGS AF: 0.304 AC: 1058 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.83
PhyloP100		0.48
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: rs3905706; hg19: chr10-28479942;