10-28089829-T-C

Variant names:

• chr10-28089829-T-C
• rs2997211
• NM_001318170.2:c.965A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318170.2(MPP7):​c.965A>G​(p.Lys322Arg) variant causes a missense change. The variant allele was found at a frequency of 0.889 in 1,509,800 control chromosomes in the GnomAD database, including 598,035 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K322Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.91 (63318 hom., cov: 30)
  • Exomes 𝑓: 0.89 (534717 hom.)
• Consequence: MPP7 NM_001318170.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86
• Publications: 31 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.712926E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	NM_001318170.2	MANE Select	c.965A>G	p.Lys322Arg	missense	Exon 12 of 17	NP_001305099.1	Q5T2T1-1
	MPP7	NM_173496.5		c.965A>G	p.Lys322Arg	missense	Exon 14 of 19	NP_775767.2	Q5T2T1-1
	MPP7	NR_134517.2		n.1300A>G		non_coding_transcript_exon	Exon 12 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	ENST00000683449.1	MANE Select	c.965A>G	p.Lys322Arg	missense	Exon 12 of 17	ENSP00000507917.1	Q5T2T1-1
	MPP7	ENST00000375719.7	TSL:1	c.965A>G	p.Lys322Arg	missense	Exon 14 of 19	ENSP00000364871.3	Q5T2T1-1
	MPP7	ENST00000496637.6	TSL:1	n.965A>G		non_coding_transcript_exon	Exon 11 of 16	ENSP00000473899.1	S4R337

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138500 AN: 151758 Hom.: 63263 Cov.: 30

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.908

GnomAD2 exomes AF: 0.909 AC: 218983 AN: 240774 AF XY: 0.908

Gnomad AFR exome AF: 0.951

Gnomad AMR exome AF: 0.955

Gnomad ASJ exome AF: 0.853

Gnomad EAS exome AF: 0.956

Gnomad FIN exome AF: 0.914

Gnomad NFE exome AF: 0.884

Gnomad OTH exome AF: 0.909

GnomAD4 exome AF: 0.887 AC: 1204169 AN: 1357930 Hom.: 534717 Cov.: 22 AF XY: 0.888 AC XY: 602502 AN XY: 678838

African (AFR) AF: 0.954 AC: 29663 AN: 31078

American (AMR) AF: 0.953 AC: 39587 AN: 41552

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 20960 AN: 24712

East Asian (EAS) AF: 0.945 AC: 36812 AN: 38962

South Asian (SAS) AF: 0.916 AC: 70517 AN: 76966

European-Finnish (FIN) AF: 0.915 AC: 47607 AN: 52014

Middle Eastern (MID) AF: 0.897 AC: 4905 AN: 5470

European-Non Finnish (NFE) AF: 0.877 AC: 903388 AN: 1030574

Other (OTH) AF: 0.896 AC: 50730 AN: 56602

GnomAD4 genome AF: 0.913 AC: 138611 AN: 151870 Hom.: 63318 Cov.: 30 AF XY: 0.916 AC XY: 67953 AN XY: 74216

African (AFR) AF: 0.951 AC: 39351 AN: 41376

American (AMR) AF: 0.932 AC: 14218 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2923 AN: 3472

East Asian (EAS) AF: 0.954 AC: 4934 AN: 5174

South Asian (SAS) AF: 0.932 AC: 4494 AN: 4822

European-Finnish (FIN) AF: 0.918 AC: 9635 AN: 10494

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.884 AC: 60057 AN: 67970

Other (OTH) AF: 0.908 AC: 1915 AN: 2108

Alfa AF: 0.891 Hom.: 259184

Bravo AF: 0.916

TwinsUK AF: 0.888 AC: 3293

ALSPAC AF: 0.872 AC: 3360

ESP6500AA AF: 0.948 AC: 4175

ESP6500EA AF: 0.877 AC: 7540

ExAC AF: 0.909 AC: 110319

Asia WGS AF: 0.952 AC: 3310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	6.7e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.8	N
PhyloP100		5.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	1.6	N
REVEL	Uncertain	0.32
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MPC		0.14
ClinPred		0.0055	T
GERP RS		5.8
Varity_R		0.11
gMVP		0.26
Mutation Taster		=99/1	polymorphism (auto)

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: rs2997211; hg19: chr10-28378758; COSMIC: COSV107426142;