1-167773343-A-G

Position:

• chr1-167773343-A-G

Variant summary

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

The NM_003953.6(MPZL1):​c.580A>G​(p.Lys194Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPZL1 NM_003953.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

Genes affected

MPZL1 (HGNC:7226): (myelin protein zero like 1) Predicted to enable structural molecule activity. Predicted to be involved in cell-cell signaling and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within positive regulation of cell migration. Located in cell surface and focal adhesion. [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=0.22472218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZL1	NM_003953.6	c.580A>G	p.Lys194Glu	missense_variant	4/6	ENST00000359523.7	NP_003944.1
MPZL1	NM_024569.5	c.580A>G	p.Lys194Glu	missense_variant	4/5		NP_078845.3
MPZL1	XM_047433610.1	c.208A>G	p.Lys70Glu	missense_variant	5/7		XP_047289566.1
MPZL1	NM_001146191.2	c.258+7594A>G		intron_variant			NP_001139663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPZL1	ENST00000359523.7	c.580A>G	p.Lys194Glu	missense_variant	4/6	1	NM_003953.6	ENSP00000352513.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Nov 25, 2024

The c.580A>G (p.K194E) alteration is located in exon 4 (coding exon 4) of the MPZL1 gene. This alteration results from a A to G substitution at nucleotide position 580, causing the lysine (K) at amino acid position 194 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T;.;T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.051
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Uncertain	0.33	D
MutationAssessor	Benign	0.90	L;L;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.27
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.19	B;B;.
Vest4		0.20
MutPred		0.35		Loss of methylation at K194 (P = 0.0023);Loss of methylation at K194 (P = 0.0023);.;
MVP		1.0
MPC		0.70
ClinPred		0.56	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-167742580;