10-28054072-T-C

Variant names:

• chr10-28054072-T-C
• rs778166162
• NM_001318170.2:c.1724A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318170.2(MPP7):​c.1724A>G​(p.His575Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MPP7 NM_001318170.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080776304).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	NM_001318170.2	MANE Select	c.1724A>G	p.His575Arg	missense	Exon 17 of 17	NP_001305099.1	Q5T2T1-1
	MPP7	NM_173496.5		c.1724A>G	p.His575Arg	missense	Exon 19 of 19	NP_775767.2	Q5T2T1-1
	MPP7	NR_134517.2		n.2193A>G		non_coding_transcript_exon	Exon 17 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	ENST00000683449.1	MANE Select	c.1724A>G	p.His575Arg	missense	Exon 17 of 17	ENSP00000507917.1	Q5T2T1-1
	MPP7	ENST00000375719.7	TSL:1	c.1724A>G	p.His575Arg	missense	Exon 19 of 19	ENSP00000364871.3	Q5T2T1-1
	MPP7	ENST00000496637.6	TSL:1	n.*493A>G		non_coding_transcript_exon	Exon 16 of 16	ENSP00000473899.1	S4R337

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000799 AC: 2 AN: 250296 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460152 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726450

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.0000225 AC: 1 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 85952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111286

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.14
Sift	Benign	0.66	T
Sift4G	Benign	0.96	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.46		Gain of phosphorylation at S576 (P = 0.1292)
MVP		0.31
MPC		0.78
ClinPred		0.32	T
GERP RS		5.4
Varity_R		0.20
gMVP		0.30
Mutation Taster		=71/29	polymorphism

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: rs778166162; hg19: chr10-28343001;