11-118260186-A-G

Variant names:

Variant summary

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

The NM_005797.4(MPZL2):c.452T>C(p.Ile151Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

MPZL2
NM_005797.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 8.03

Variant links:

Genes affected

MPZL2 (HGNC:3496): (myelin protein zero like 2) Thymus development depends on a complex series of interactions between thymocytes and the stromal component of the organ. Epithelial V-like antigen (EVA) is expressed in thymus epithelium and strongly downregulated by thymocyte developmental progression. This gene is expressed in the thymus and in several epithelial structures early in embryogenesis. It is highly homologous to the myelin protein zero and, in thymus-derived epithelial cell lines, is poorly soluble in nonionic detergents, strongly suggesting an association to the cytoskeleton. Its capacity to mediate cell adhesion through a homophilic interaction and its selective regulation by T cell maturation might imply the participation of EVA in the earliest phases of thymus organogenesis. The protein bears a characteristic V-type domain and two potential N-glycosylation sites in the extracellular domain; a putative serine phosphorylation site for casein kinase 2 is also present in the cytoplasmic tail. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MPZL2 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=0.40866834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPZL2	NM_005797.4 link	c.452T>C	p.Ile151Thr	missense_variant	Exon 4 of 6	ENST00000278937.7	NP_005788.1	O60487A0A024R3K1
MPZL2	NM_144765.3 link	c.452T>C	p.Ile151Thr	missense_variant	Exon 4 of 5		NP_658911.1	O60487A0A024R3K1
MPZL2	XM_047426229.1 link	c.388T>C	p.Ser130Pro	missense_variant	Exon 4 of 4		XP_047282185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MPZL2	ENST00000278937.7 link	c.452T>C	p.Ile151Thr	missense_variant	Exon 4 of 6	1	NM_005797.4	ENSP00000278937.2	O60487
MPZL2	ENST00000438295.2 link	c.452T>C	p.Ile151Thr	missense_variant	Exon 4 of 5	1		ENSP00000408362.2	O60487
MPZL2	ENST00000529376.5 link	n.582T>C		non_coding_transcript_exon_variant	Exon 4 of 4	2
MPZL2	ENST00000534175.6 link	n.500T>C		non_coding_transcript_exon_variant	Exon 3 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000677

AC:

AN:

251054

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000732

AC:

107

AN:

1461720

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000845

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.452T>C (p.I151T) alteration is located in exon 4 (coding exon 4) of the MPZL2 gene. This alteration results from a T to C substitution at nucleotide position 452, causing the isoleucine (I) at amino acid position 151 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Jun 20, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.86

.;D

M_CAP

Benign

0.081

MetaRNN

Benign

0.41

T;T

MetaSVM

Uncertain

0.75

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.63

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.96

D;D

Vest4

0.58

MVP

0.56

MPC

0.17

ClinPred

0.16

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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