chr10-28055828-G-C

Variant names:

• chr10-28055828-G-C
• rs10508729
• NM_001318170.2:c.1551+652C>G

Variant summary

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

The NM_001318170.2(MPP7):​c.1551+652C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 152,194 control chromosomes in the GnomAD database, including 98 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 0.024 (98 hom., cov: 32)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 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.1551+652C>G		intron	N/A	NP_001305099.1	Q5T2T1-1
	MPP7	NM_173496.5		c.1551+652C>G		intron	N/A	NP_775767.2	Q5T2T1-1
	MPP7	NR_134517.2		n.2020+652C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	ENST00000683449.1	MANE Select	c.1551+652C>G		intron	N/A	ENSP00000507917.1	Q5T2T1-1
	MPP7	ENST00000375719.7	TSL:1	c.1551+652C>G		intron	N/A	ENSP00000364871.3	Q5T2T1-1
	MPP7	ENST00000496637.6	TSL:1	n.*320+652C>G		intron	N/A	ENSP00000473899.1	S4R337

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3686 AN: 152076 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00863

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0243 AC: 3692 AN: 152194 Hom.: 98 Cov.: 32 AF XY: 0.0265 AC XY: 1970 AN XY: 74426

African (AFR) AF: 0.0377 AC: 1567 AN: 41534

American (AMR) AF: 0.0192 AC: 293 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.118 AC: 611 AN: 5180

South Asian (SAS) AF: 0.0997 AC: 480 AN: 4816

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00863 AC: 587 AN: 67998

Other (OTH) AF: 0.0142 AC: 30 AN: 2110

Alfa AF: 0.00283 Hom.: 0

Bravo AF: 0.0244

Asia WGS AF: 0.0910 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.34
PhyloP100		0.49
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: rs10508729; hg19: chr10-28344757;