11-30430634-T-C

Variant names:

• chr11-30430634-T-C
• rs514644
• NM_001584.3:c.537-13001A>G

Variant summary

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

The NM_001584.3(MPPED2):​c.537-13001A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,168 control chromosomes in the GnomAD database, including 9,715 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 0.31 (9715 hom., cov: 33)
• Consequence: MPPED2 NM_001584.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPPED2	NM_001584.3	c.537-13001A>G		intron_variant	Intron 4 of 6	ENST00000358117.10	NP_001575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPPED2	ENST00000358117.10	c.537-13001A>G		intron_variant	Intron 4 of 6	1	NM_001584.3	ENSP00000350833.4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47172 AN: 152050 Hom.: 9683 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.311 AC: 47250 AN: 152168 Hom.: 9715 Cov.: 33 AF XY: 0.311 AC XY: 23158 AN XY: 74398

African (AFR) AF: 0.573 AC: 23775 AN: 41502

American (AMR) AF: 0.289 AC: 4416 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3472

East Asian (EAS) AF: 0.433 AC: 2240 AN: 5170

South Asian (SAS) AF: 0.406 AC: 1957 AN: 4818

European-Finnish (FIN) AF: 0.127 AC: 1350 AN: 10604

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11779 AN: 67988

Other (OTH) AF: 0.302 AC: 639 AN: 2116

Alfa AF: 0.222 Hom.: 19098

Bravo AF: 0.331

Asia WGS AF: 0.390 AC: 1354 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.36
PhyloP100		-2.5
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: rs514644; hg19: chr11-30452181;