22-43425116-T-C

Position:

• chr22-43425116-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001044370.2(MPPED1):​c.131T>C​(p.Ile44Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPPED1 NM_001044370.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

Genes affected

MPPED1 (HGNC:1306): (metallophosphoesterase domain containing 1) Predicted to enable hydrolase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096898824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPPED1	NM_001044370.2	c.131T>C	p.Ile44Thr	missense_variant	2/7	ENST00000443721.2	NP_001037835.1
MPPED1	NM_001362786.2	c.131T>C	p.Ile44Thr	missense_variant	2/7		NP_001349715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPPED1	ENST00000443721.2	c.131T>C	p.Ile44Thr	missense_variant	2/7	2	NM_001044370.2	ENSP00000400686	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.131T>C (p.I44T) alteration is located in exon (coding exon ) of the MPPED1 gene. This alteration results from a T to C substitution at nucleotide position 131, causing the isoleucine (I) at amino acid position 44 to be replaced by a threonine (T). 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	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.81
DEOGEN2	Benign	0.032	T;.;T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.81	.;T;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.097	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N;.;N;.
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.81	N;N;N;N
REVEL	Benign	0.046
Sift	Benign	0.68	T;T;T;T
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.0010	B;.;B;.
Vest4		0.23
MVP		0.57
MPC		0.96
ClinPred		0.31	T
GERP RS		5.2
Varity_R		0.14
gMVP		0.25

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: chr22-43821122;