NM_023075.6:c.390+622T>C

Variant names:

• chr18-11892846-A-G
• rs3974590
• NM_023075.6:c.390+622T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023075.6. 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
	MPPE1	NM_023075.6	MANE Select	c.390+622T>C		intron	N/A	NP_075563.3
	MPPE1	NM_001330563.2		c.390+622T>C		intron	N/A	NP_001317492.1
	MPPE1	NM_001242904.2		c.390+622T>C		intron	N/A	NP_001229833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPPE1	ENST00000588072.6	TSL:1 MANE Select	c.390+622T>C		intron	N/A	ENSP00000465894.1
	MPPE1	ENST00000309976.13	TSL:1	c.390+622T>C		intron	N/A	ENSP00000311200.9
	MPPE1	ENST00000317235.11	TSL:1	c.390+622T>C		intron	N/A	ENSP00000327257.6

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

African (AFR) AF: 0.512 AC: 21206 AN: 41416

American (AMR) AF: 0.307 AC: 4685 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1405 AN: 3466

East Asian (EAS) AF: 0.515 AC: 2651 AN: 5150

South Asian (SAS) AF: 0.371 AC: 1790 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2376 AN: 10550

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18505 AN: 67986

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.307 Hom.: 10272

Bravo AF: 0.364

Asia WGS AF: 0.443 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.42
PhyloP100		-0.98
Mutation Taster		=100/0	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: rs3974590; hg19: chr18-11892845;