rs3974590

chr18-11892846-A-G

Variant summary

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

The NM_023075.6(MPPE1):c.390+622T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,968 control chromosomes in the GnomAD database, including 10,487 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 0.35 (10487 hom., cov: 31)
• Consequence: MPPE1 NM_023075.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPPE1	NM_023075.6	c.390+622T>C		intron_variant		ENST00000588072.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPPE1	ENST00000588072.6	c.390+622T>C		intron_variant		1	NM_023075.6	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53702 AN: 151850 Hom.: 10465 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.354 AC: 53775 AN: 151968 Hom.: 10487 Cov.: 31 AF XY: 0.353 AC XY: 26242 AN XY: 74256

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.379

Alfa AF: 0.300 Hom.: 7519

Bravo AF: 0.364

Asia WGS AF: 0.443 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.43
Dann	Benign	0.42

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: rs3974590; hg19: chr18-11892845;