NM_001318170.2:c.1129G>T

Variant names:

• chr10-28069847-C-A
• rs578191058
• NM_001318170.2:c.1129G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318170.2(MPP7):​c.1129G>T​(p.Val377Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V377M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPP7 NM_001318170.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18899179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.1129G>T	p.Val377Leu	missense_variant	Exon 13 of 17	ENST00000683449.1	NP_001305099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000683449.1	c.1129G>T	p.Val377Leu	missense_variant	Exon 13 of 17		NM_001318170.2	ENSP00000507917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;T;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;.;.;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.090	N;N;N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.40	N;N;N;N
REVEL	Benign	0.078
Sift	Benign	0.33	T;T;T;T
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.0030	B;B;B;.
Vest4		0.52
MutPred		0.43		Loss of MoRF binding (P = 0.1251);Loss of MoRF binding (P = 0.1251);Loss of MoRF binding (P = 0.1251);.;
MVP		0.37
MPC		0.38
ClinPred		0.86	D
GERP RS		4.9
Varity_R		0.079
gMVP		0.55

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: rs578191058; hg19: chr10-28358776;