chr17-43800798-A-C

Variant names:

• chr17-43800798-A-C
• rs8077889
• NM_001932.6:c.*903T>G

Variant summary

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

The NM_001932.6(MPP3):​c.*903T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,030 control chromosomes in the GnomAD database, including 2,971 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.

• Frequency:
  • Genomes: 𝑓 0.19 (2971 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MPP3 NM_001932.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 64 publications found

Genes affected

MPP3 (HGNC:7221): (MAGUK p55 scaffold protein 3) This gene product is a member of a family of membrane-associated proteins termed MAGUKs (membrane-associated guanylate kinase homologs). MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intracellular junctions. This protein contains a conserved sequence, called the SH3 (src homology 3) motif, found in several other proteins that associate with the cytoskeleton and are suspected to play important roles in signal transduction. Alternatively spliced transcript variants have been identified. One transcript variant is experimentally supported, but it doesn't encode a protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001932.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP3	NM_001932.6	MANE Select	c.*903T>G		downstream_gene	N/A	NP_001923.2
	MPP3	NM_001330233.2		c.*903T>G		downstream_gene	N/A	NP_001317162.1
	MPP3	NM_001353080.2		c.*903T>G		downstream_gene	N/A	NP_001340009.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP3	ENST00000398389.9	TSL:1 MANE Select	c.*903T>G		downstream_gene	N/A	ENSP00000381425.4
	MPP3	ENST00000398393.5	TSL:1	c.*903T>G		downstream_gene	N/A	ENSP00000381430.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29158 AN: 151912 Hom.: 2964 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.206

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.192 AC: 29197 AN: 152030 Hom.: 2971 Cov.: 32 AF XY: 0.192 AC XY: 14248 AN XY: 74312

African (AFR) AF: 0.186 AC: 7706 AN: 41462

American (AMR) AF: 0.151 AC: 2310 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5184

South Asian (SAS) AF: 0.174 AC: 840 AN: 4814

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10562

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14416 AN: 67960

Other (OTH) AF: 0.203 AC: 428 AN: 2106

Alfa AF: 0.203 Hom.: 13027

Bravo AF: 0.187

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		-0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8077889; hg19: chr17-41878166;