11-30580311-G-T

Variant names:

• chr11-30580311-G-T
• NM_001584.3:c.63C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001584.3(MPPED2):​c.63C>A​(p.Asn21Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MPPED2 NM_001584.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2917347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPPED2	NM_001584.3	c.63C>A	p.Asn21Lys	missense_variant	Exon 2 of 7	ENST00000358117.10	NP_001575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPPED2	ENST00000358117.10	c.63C>A	p.Asn21Lys	missense_variant	Exon 2 of 7	1	NM_001584.3	ENSP00000350833.4
MPPED2	ENST00000448418.6	c.63C>A	p.Asn21Lys	missense_variant	Exon 2 of 7	1		ENSP00000388258.2
MPPED2	ENST00000526437.5	n.63C>A		non_coding_transcript_exon_variant	Exon 2 of 8	1		ENSP00000432469.1
MPPED2	ENST00000528686.2	c.63C>A	p.Asn21Lys	missense_variant	Exon 2 of 3	4		ENSP00000431805.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.63C>A (p.N21K) alteration is located in exon 1 (coding exon 1) of the MPPED2 gene. This alteration results from a C to A substitution at nucleotide position 63, causing the asparagine (N) at amino acid position 21 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	.;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	N;N;D
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D;T;D
Sift4G	Benign	0.23	T;T;.
Polyphen		0.99	.;D;.
Vest4		0.89
MutPred		0.32		Gain of ubiquitination at N21 (P = 0.0075);Gain of ubiquitination at N21 (P = 0.0075);Gain of ubiquitination at N21 (P = 0.0075);
MVP		0.15
MPC		1.3
ClinPred		0.85	D
GERP RS		2.8
Varity_R		0.22
gMVP		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-30601858;