11-30467480-G-A

Variant names:

• chr11-30467480-G-A
• rs1026477
• NM_001584.3:c.536+27816C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001584.3(MPPED2):​c.536+27816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,990 control chromosomes in the GnomAD database, including 16,706 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 0.45 (16706 hom., cov: 31)
• Consequence: MPPED2 NM_001584.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• Publications: 4 publications found

Genes affected

MPPED2 (HGNC:1180): (metallophosphoesterase domain containing 2) Predicted to enable manganese ion binding activity; phosphoric diester hydrolase activity; and purine ribonucleotide binding activity. [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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001584.3. 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
	MPPED2	NM_001584.3	MANE Select	c.536+27816C>T		intron	N/A	NP_001575.1
	MPPED2	NM_001377952.1		c.536+27816C>T		intron	N/A	NP_001364881.1
	MPPED2	NM_001377953.1		c.536+27816C>T		intron	N/A	NP_001364882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPPED2	ENST00000358117.10	TSL:1 MANE Select	c.536+27816C>T		intron	N/A	ENSP00000350833.4
	MPPED2	ENST00000448418.6	TSL:1	c.536+27816C>T		intron	N/A	ENSP00000388258.2
	MPPED2	ENST00000526437.5	TSL:1	n.*280+27816C>T		intron	N/A	ENSP00000432469.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68229 AN: 151872 Hom.: 16695 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.449 AC: 68277 AN: 151990 Hom.: 16706 Cov.: 31 AF XY: 0.453 AC XY: 33639 AN XY: 74284

African (AFR) AF: 0.238 AC: 9868 AN: 41476

American (AMR) AF: 0.590 AC: 9018 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3472

East Asian (EAS) AF: 0.553 AC: 2837 AN: 5126

South Asian (SAS) AF: 0.372 AC: 1792 AN: 4816

European-Finnish (FIN) AF: 0.577 AC: 6098 AN: 10566

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35600 AN: 67930

Other (OTH) AF: 0.464 AC: 979 AN: 2108

Alfa AF: 0.501 Hom.: 34416

Bravo AF: 0.449

Asia WGS AF: 0.474 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.60
PhyloP100		3.2
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: rs1026477; hg19: chr11-30489027;