11-30486561-T-C

Variant names:

• chr11-30486561-T-C
• rs545610
• NM_001584.3:c.536+8735A>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.536+8735A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,132 control chromosomes in the GnomAD database, including 42,878 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 0.74 (42878 hom., cov: 32)
• Consequence: MPPED2 NM_001584.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPPED2	NM_001584.3	MANE Select	c.536+8735A>G		intron	N/A	NP_001575.1	Q15777-1
	MPPED2	NM_001377952.1		c.536+8735A>G		intron	N/A	NP_001364881.1	Q15777-1
	MPPED2	NM_001377953.1		c.536+8735A>G		intron	N/A	NP_001364882.1	Q15777-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPPED2	ENST00000358117.10	TSL:1 MANE Select	c.536+8735A>G		intron	N/A	ENSP00000350833.4	Q15777-1
	MPPED2	ENST00000448418.6	TSL:1	c.536+8735A>G		intron	N/A	ENSP00000388258.2	Q15777-2
	MPPED2	ENST00000526437.5	TSL:1	n.*280+8735A>G		intron	N/A	ENSP00000432469.1	E9PQW8

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113014 AN: 152014 Hom.: 42831 Cov.: 32

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.744 AC: 113121 AN: 152132 Hom.: 42878 Cov.: 32 AF XY: 0.743 AC XY: 55258 AN XY: 74344

African (AFR) AF: 0.899 AC: 37322 AN: 41534

American (AMR) AF: 0.728 AC: 11127 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2369 AN: 3470

East Asian (EAS) AF: 0.923 AC: 4768 AN: 5168

South Asian (SAS) AF: 0.752 AC: 3626 AN: 4822

European-Finnish (FIN) AF: 0.625 AC: 6583 AN: 10540

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44953 AN: 67984

Other (OTH) AF: 0.745 AC: 1574 AN: 2114

Alfa AF: 0.694 Hom.: 164257

Bravo AF: 0.756

Asia WGS AF: 0.829 AC: 2883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.38
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: rs545610; hg19: chr11-30508108;