10-28328706-C-G

Variant names:

• chr10-28328706-C-G
• rs1148186
• ENST00000893162.1:c.-132+6164G>C

Variant summary

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

The ENST00000893162.1(MPP7):​c.-132+6164G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,724 control chromosomes in the GnomAD database, including 6,883 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 (6883 hom., cov: 31)
• Consequence: MPP7 ENST00000893162.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000893162.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	ENST00000893162.1		c.-132+6164G>C		intron	N/A	ENSP00000563221.1
	MPP7	ENST00000957212.1		c.-235+6164G>C		intron	N/A	ENSP00000627271.1
	MPP7	ENST00000441595.2	TSL:5	c.-132+1223G>C		intron	N/A	ENSP00000398319.1	U5GXS2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39027 AN: 151606 Hom.: 6859 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.0386

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.258 AC: 39096 AN: 151724 Hom.: 6883 Cov.: 31 AF XY: 0.254 AC XY: 18854 AN XY: 74126

African (AFR) AF: 0.502 AC: 20740 AN: 41354

American (AMR) AF: 0.161 AC: 2450 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3460

East Asian (EAS) AF: 0.0510 AC: 264 AN: 5174

South Asian (SAS) AF: 0.170 AC: 818 AN: 4818

European-Finnish (FIN) AF: 0.196 AC: 2057 AN: 10486

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11426 AN: 67908

Other (OTH) AF: 0.230 AC: 487 AN: 2114

Alfa AF: 0.151 Hom.: 1053

Bravo AF: 0.266

Asia WGS AF: 0.117 AC: 406 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		0.089

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1148186;

hg19: chr10-28617635;