rs593713

Positions:

• chr18-11887658-G-A

Variant summary

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

The NM_023075.6(MPPE1):​c.570-633C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,010 control chromosomes in the GnomAD database, including 16,696 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 0.42 (16696 hom., cov: 32)
• Consequence: MPPE1 NM_023075.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

Genes affected

MPPE1 (HGNC:15988): (metallophosphoesterase 1) Predicted to enable GPI anchor binding activity; GPI-mannose ethanolamine phosphate phosphodiesterase activity; and manganese ion binding activity. Involved in GPI anchor biosynthetic process. Located in Golgi apparatus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPPE1	NM_023075.6	c.570-633C>T		intron_variant		ENST00000588072.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPPE1	ENST00000588072.6	c.570-633C>T		intron_variant		1	NM_023075.6	P1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63670 AN: 151892 Hom.: 16651 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.424

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63771 AN: 152010 Hom.: 16696 Cov.: 32 AF XY: 0.418 AC XY: 31020 AN XY: 74292

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.431

Alfa AF: 0.306 Hom.: 16204

Bravo AF: 0.443

Asia WGS AF: 0.503 AC: 1750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs593713; hg19: chr18-11887657;