rs871044

Variant names:

• chr18-11907375-A-G
• rs871044
• NM_023075.6:c.-200+826T>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.-200+826T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,018 control chromosomes in the GnomAD database, including 19,274 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 0.49 (19274 hom., cov: 32)
• Consequence: MPPE1 NM_023075.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 8 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPPE1	NM_023075.6	MANE Select	c.-200+826T>C		intron	N/A	NP_075563.3
	MPPE1	NM_001330563.2		c.-200+826T>C		intron	N/A	NP_001317492.1	A0A0A0MR93
	MPPE1	NM_001242904.2		c.-93+826T>C		intron	N/A	NP_001229833.1	Q53F39-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPPE1	ENST00000588072.6	TSL:1 MANE Select	c.-200+826T>C		intron	N/A	ENSP00000465894.1	Q53F39-1
	MPPE1	ENST00000309976.13	TSL:1	c.-93+826T>C		intron	N/A	ENSP00000311200.9	Q53F39-4
	MPPE1	ENST00000317235.11	TSL:1	c.-200+826T>C		intron	N/A	ENSP00000327257.6	Q53F39-4

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74265 AN: 151900 Hom.: 19248 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.489 AC: 74344 AN: 152018 Hom.: 19274 Cov.: 32 AF XY: 0.486 AC XY: 36118 AN XY: 74306

African (AFR) AF: 0.672 AC: 27845 AN: 41460

American (AMR) AF: 0.432 AC: 6589 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1870 AN: 3472

East Asian (EAS) AF: 0.582 AC: 3016 AN: 5180

South Asian (SAS) AF: 0.507 AC: 2442 AN: 4816

European-Finnish (FIN) AF: 0.343 AC: 3613 AN: 10546

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27261 AN: 67974

Other (OTH) AF: 0.504 AC: 1061 AN: 2104

Alfa AF: 0.432 Hom.: 50956

Bravo AF: 0.502

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.75
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs871044; hg19: chr18-11907374;