Variant 1-167722165-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003953.6(MPZL1):c.14C>A(p.Ala5Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,236,270 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 0 hom. )

Consequence

MPZL1
NM_003953.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0630

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3276676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MPZL1	NM_003953.6 linkuse as main transcript	c.14C>A	p.Ala5Asp	missense_variant	1/6	ENST00000359523.7	NP_003944.1
MPZL1	NM_024569.5 linkuse as main transcript	c.14C>A	p.Ala5Asp	missense_variant	1/5		NP_078845.3
MPZL1	NM_001146191.2 linkuse as main transcript	c.14C>A	p.Ala5Asp	missense_variant	1/3		NP_001139663.1
MPZL1	XM_047433610.1 linkuse as main transcript	c.-441C>A		5_prime_UTR_variant	1/7		XP_047289566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPZL1	ENST00000359523.7 linkuse as main transcript	c.14C>A	p.Ala5Asp	missense_variant	1/6	1	NM_003953.6	ENSP00000352513	P3	O95297-1

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000526

AC:

570

AN:

1084338

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

272

AN XY:

512580

show subpopulations

Gnomad4 AFR exome

AF:

0.0000872

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000698

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000604

Gnomad4 OTH exome

AF:

0.000252

GnomAD4 genome

AF:

0.000211

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000200

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

Dec 27, 2023

The c.14C>A (p.A5D) alteration is located in exon 1 (coding exon 1) of the MPZL1 gene. This alteration results from a C to A substitution at nucleotide position 14, causing the alanine (A) at amino acid position 5 to be replaced by an aspartic acid (D). 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

0.22

BayesDel_addAF

Benign

-0.0036

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.023

T;.;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.70

T;T;T

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.90

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.67

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.014

D;D;D

Sift4G

Benign

0.10

T;T;D

Polyphen

0.028

B;.;B

Vest4

0.29

MutPred

0.15

Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);

MVP

0.99

MPC

0.63

ClinPred

0.96

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.32

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