Variant 1-167773302-C-T 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.539C>T(p.Thr180Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MPZL1
NM_003953.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0650

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07333645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MPZL1	NM_003953.6 linkuse as main transcript	c.539C>T	p.Thr180Ile	missense_variant	4/6	ENST00000359523.7	NP_003944.1
MPZL1	NM_024569.5 linkuse as main transcript	c.539C>T	p.Thr180Ile	missense_variant	4/5		NP_078845.3
MPZL1	XM_047433610.1 linkuse as main transcript	c.167C>T	p.Thr56Ile	missense_variant	5/7		XP_047289566.1
MPZL1	NM_001146191.2 linkuse as main transcript	c.258+7553C>T		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.539C>T	p.Thr180Ile	missense_variant	4/6	1	NM_003953.6	ENSP00000352513	P3	O95297-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461418

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000567

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 09, 2023

The c.539C>T (p.T180I) alteration is located in exon 4 (coding exon 4) of the MPZL1 gene. This alteration results from a C to T substitution at nucleotide position 539, causing the threonine (T) at amino acid position 180 to be replaced by an isoleucine (I). 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

0.083

BayesDel_addAF

Benign

-0.0056

BayesDel_noAF

Benign

-0.25

CADD

Benign

4.9

DANN

Benign

0.12

DEOGEN2

Benign

0.021

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.073

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.34

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.50

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.50

T;T;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.15

MutPred

0.41

Loss of MoRF binding (P = 0.1721);Loss of MoRF binding (P = 0.1721);.;

MVP

0.82

MPC

0.45

ClinPred

0.18

GERP RS

1.3

Varity_R

0.024

gMVP

0.50

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

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