10-28135248-G-A

Variant names:

• chr10-28135248-G-A
• rs4317882
• NM_001318170.2:c.316-3557C>T

Variant summary

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

The NM_001318170.2(MPP7):​c.316-3557C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 152,134 control chromosomes in the GnomAD database, including 1,249 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 0.098 (1249 hom., cov: 32)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.316-3557C>T		intron_variant	Intron 5 of 16	ENST00000683449.1	NP_001305099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000683449.1	c.316-3557C>T		intron_variant	Intron 5 of 16		NM_001318170.2	ENSP00000507917.1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14910 AN: 152016 Hom.: 1236 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0430

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.0983 AC: 14948 AN: 152134 Hom.: 1249 Cov.: 32 AF XY: 0.107 AC XY: 7929 AN XY: 74382

African (AFR) AF: 0.117 AC: 4875 AN: 41536

American (AMR) AF: 0.128 AC: 1956 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3468

East Asian (EAS) AF: 0.419 AC: 2152 AN: 5136

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4826

European-Finnish (FIN) AF: 0.125 AC: 1326 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0430 AC: 2924 AN: 67996

Other (OTH) AF: 0.0981 AC: 207 AN: 2110

Alfa AF: 0.0695 Hom.: 373

Bravo AF: 0.101

Asia WGS AF: 0.389 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.66
DANN	Benign	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

Publications

LitVar

Other links and lift over

dbSNP: rs4317882; hg19: chr10-28424177;