rs8077889

Positions:

• chr17-43800798-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 17-43800798-A-C 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPP3	NM_001932.6			downstream_gene_variant		ENST00000398389.9	NP_001923.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPP3	ENST00000398389.9			downstream_gene_variant		1	NM_001932.6	ENSP00000381425	P1
MPP3	ENST00000398393.5			downstream_gene_variant		1		ENSP00000381430

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

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

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.203

Alfa AF: 0.207 Hom.: 6194

Bravo AF: 0.187

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8077889; hg19: chr17-41878166;