chr10-28211458-T-G

Variant names:

• chr10-28211458-T-G
• rs113263669
• NM_001318170.2:c.38-9187A>C

Variant summary

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

The NM_001318170.2(MPP7):​c.38-9187A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 134,822 control chromosomes in the GnomAD database, including 123 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 0.032 (123 hom., cov: 30)
• Consequence: MPP7 NM_001318170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.38-9187A>C		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.38-9187A>C		intron_variant	Intron 2 of 16		NM_001318170.2	ENSP00000507917.1

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4303 AN: 134764 Hom.: 124 Cov.: 30

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.00743

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00467

Gnomad FIN AF: 0.00300

Gnomad MID AF: 0.0336

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0319 AC: 4301 AN: 134822 Hom.: 123 Cov.: 30 AF XY: 0.0308 AC XY: 2022 AN XY: 65604

African (AFR) AF: 0.0857 AC: 2960 AN: 34544

American (AMR) AF: 0.0293 AC: 376 AN: 12850

Ashkenazi Jewish (ASJ) AF: 0.00743 AC: 24 AN: 3228

East Asian (EAS) AF: 0.00 AC: 0 AN: 3742

South Asian (SAS) AF: 0.00467 AC: 20 AN: 4280

European-Finnish (FIN) AF: 0.00300 AC: 28 AN: 9320

Middle Eastern (MID) AF: 0.0219 AC: 6 AN: 274

European-Non Finnish (NFE) AF: 0.0128 AC: 816 AN: 63854

Other (OTH) AF: 0.0269 AC: 50 AN: 1858

Alfa AF: 0.00544 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.40
PhyloP100		-0.52
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: rs113263669; hg19: chr10-28500387; COSMIC: COSV61729736;