Genetic Variant MPP7:c.316-3557C>T (chr10-28135248-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

4 publications found

Variant links:

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]

MPP7 links:

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new If you want to explore the variant's impact on the transcript NM_001318170.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPP7	NM_001318170.2	MANE Select	c.316-3557C>T	intron	N/A	NP_001305099.1	Q5T2T1-1
MPP7	NM_173496.5		c.316-3557C>T	intron	N/A	NP_775767.2	Q5T2T1-1
MPP7	NR_134517.2		n.651-3557C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPP7	ENST00000683449.1	MANE Select	c.316-3557C>T	intron	N/A	ENSP00000507917.1	Q5T2T1-1
MPP7	ENST00000375719.7	TSL:1	c.316-3557C>T	intron	N/A	ENSP00000364871.3	Q5T2T1-1
MPP7	ENST00000496637.6	TSL:1	n.316-3557C>T	intron	N/A	ENSP00000473899.1	S4R337

Frequencies

GnomAD3 genomes

AF:

0.0981

AC:

14910

AN:

152016

Hom.:

1236

Cov.:

show subpopulations

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.:

AF XY:

0.107

AC XY:

7929

AN XY:

74382

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0430

AC:

2924

AN:

67996

Other (OTH)

AF:

0.0981

AC:

207

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

630

1259

1889

2518

3148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.66

(source)

DANN

Benign

0.48

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over