chr10-28216015-T-C

Variant names:

• chr10-28216015-T-C
• rs11006923
• NM_001318170.2:c.38-13744A>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.38-13744A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 152,014 control chromosomes in the GnomAD database, including 1,041 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 0.082 (1041 hom., cov: 31)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.38-13744A>G		intron_variant	Intron 2 of 16	ENST00000683449.1	NP_001305099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000683449.1	c.38-13744A>G		intron_variant	Intron 2 of 16		NM_001318170.2	ENSP00000507917.1

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12453 AN: 151896 Hom.: 1025 Cov.: 31

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0916

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

GnomAD4 genome AF: 0.0821 AC: 12485 AN: 152014 Hom.: 1041 Cov.: 31 AF XY: 0.0914 AC XY: 6793 AN XY: 74286

African (AFR) AF: 0.0392 AC: 1627 AN: 41484

American (AMR) AF: 0.122 AC: 1862 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3466

East Asian (EAS) AF: 0.407 AC: 2098 AN: 5154

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4804

European-Finnish (FIN) AF: 0.135 AC: 1424 AN: 10548

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3570 AN: 67994

Other (OTH) AF: 0.0991 AC: 209 AN: 2108

Alfa AF: 0.0704 Hom.: 1353

Bravo AF: 0.0796

Asia WGS AF: 0.384 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.087
DANN	Benign	0.42
PhyloP100		-3.1
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: rs11006923; hg19: chr10-28504944;