Variant 1-167773314-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003953.6(MPZL1):c.551G>A(p.Ser184Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MPZL1
NM_003953.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0810

Variant links:

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]

MPZL1 links:

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ACMG classification

Classification made for transcript

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=0.11216819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MPZL1	NM_003953.6 linkuse as main transcript	c.551G>A	p.Ser184Asn	missense_variant	4/6	ENST00000359523.7	NP_003944.1
MPZL1	NM_024569.5 linkuse as main transcript	c.551G>A	p.Ser184Asn	missense_variant	4/5		NP_078845.3
MPZL1	XM_047433610.1 linkuse as main transcript	c.179G>A	p.Ser60Asn	missense_variant	5/7		XP_047289566.1
MPZL1	NM_001146191.2 linkuse as main transcript	c.258+7565G>A		intron_variant			NP_001139663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPZL1	ENST00000359523.7 linkuse as main transcript	c.551G>A	p.Ser184Asn	missense_variant	4/6	1	NM_003953.6	ENSP00000352513	P3	O95297-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461644

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.551G>A (p.S184N) alteration is located in exon 4 (coding exon 4) of the MPZL1 gene. This alteration results from a G to A substitution at nucleotide position 551, causing the serine (S) at amino acid position 184 to be replaced by an asparagine (N). 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

0.30

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.060

T;.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

0.90

D;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.046

D;D;D

Sift4G

Benign

0.35

T;T;T

Polyphen

0.18

B;B;.

Vest4

0.38

MVP

0.90

MPC

0.45

ClinPred

0.16

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over