Genetic Variant NM_001318170.2:c.1128C>T (chr10-28069848-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001318170.2(MPP7):c.1128C>T(p.Pro376Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000759 in 1,613,190 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 7 hom. )

Consequence

MPP7
NM_001318170.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.248

Publications

2 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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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 10-28069848-G-A is Benign according to our data. Variant chr10-28069848-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3388156.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.248 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	NM_001318170.2 link	c.1128C>T	p.Pro376Pro	synonymous_variant	Exon 13 of 17	ENST00000683449.1	NP_001305099.1	Q5T2T1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000683449.1 link	c.1128C>T	p.Pro376Pro	synonymous_variant	Exon 13 of 17		NM_001318170.2	ENSP00000507917.1		Q5T2T1-1

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

514

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00243

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00108

AC:

270

AN:

250610

AF XY:

0.000753

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000485

AC:

708

AN:

1461182

Hom.:

Cov.:

AF XY:

0.000442

AC XY:

321

AN XY:

726880

show subpopulations

African (AFR)

AF:

0.0128

AC:

428

AN:

33458

American (AMR)

AF:

0.00183

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000116

AC:

AN:

86130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000855

AC:

AN:

1111566

Other (OTH)

AF:

0.00124

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00340

AC:

517

AN:

152008

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0111

AC:

459

AN:

41460

American (AMR)

AF:

0.00243

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67994

Other (OTH)

AF:

0.00711

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00412

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MPP7: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.4

(source)

DANN

Benign

0.72

PhyloP100

-0.25

Mutation Taster

=99/1

polymorphism

(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

Publications

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NM_001318170.2:c.1128C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over