NM_001318170.2:c.965A>C

Variant names:

• chr10-28089829-T-G
• NM_001318170.2:c.965A>C

Variant summary

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

The NM_001318170.2(MPP7):​c.965A>C​(p.Lys322Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000735 in 1,361,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. K322R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: MPP7 NM_001318170.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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=0.25628358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	NM_001318170.2	c.965A>C	p.Lys322Thr	missense_variant	Exon 12 of 17	ENST00000683449.1	NP_001305099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000683449.1	c.965A>C	p.Lys322Thr	missense_variant	Exon 12 of 17		NM_001318170.2	ENSP00000507917.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1361308 Hom.: 0 Cov.: 22 AF XY: 0.00000147 AC XY: 1 AN XY: 680384

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000241

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.090
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D;.;.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.0	N;N;N;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.018	D;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D
Polyphen		0.010	B;B;B;.
Vest4		0.30
MutPred		0.26		Loss of methylation at K322 (P = 0.0121);Loss of methylation at K322 (P = 0.0121);Loss of methylation at K322 (P = 0.0121);.;
MVP		0.89
MPC		0.21
ClinPred		0.85	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-28378758;