11-118260201-A-G

Position:

chr11-118260201-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting

The NM_005797.4(MPZL2):c.437T>C(p.Val146Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000085 in 1,612,038 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 2 hom. )

Consequence

MPZL2
NM_005797.4 missense, splice_region

Scores

Splicing: ADA: 0.00006907

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.27

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:

MPZL2 (HGNC:):

MPZL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005107552).

BP6

Variant 11-118260201-A-G is Benign according to our data. Variant chr11-118260201-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3358825.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZL2	NM_005797.4 linkuse as main transcript	c.437T>C	p.Val146Ala	missense_variant, splice_region_variant	4/6	ENST00000278937.7	NP_005788.1	O60487A0A024R3K1
MPZL2	NM_144765.3 linkuse as main transcript	c.437T>C	p.Val146Ala	missense_variant, splice_region_variant	4/5		NP_658911.1	O60487A0A024R3K1
MPZL2	XM_047426229.1 linkuse as main transcript	c.373T>C	p.Tyr125His	missense_variant, splice_region_variant	4/4		XP_047282185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MPZL2	ENST00000278937.7 linkuse as main transcript	c.437T>C	p.Val146Ala	missense_variant, splice_region_variant	4/6	1	NM_005797.4	ENSP00000278937.2	O60487
MPZL2	ENST00000438295.2 linkuse as main transcript	c.437T>C	p.Val146Ala	missense_variant, splice_region_variant	4/5	1		ENSP00000408362.2	O60487
MPZL2	ENST00000529376.5 linkuse as main transcript	n.567T>C		splice_region_variant, non_coding_transcript_exon_variant	4/4	2
MPZL2	ENST00000534175.6 linkuse as main transcript	n.485T>C		splice_region_variant, non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152242

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:

0.00327

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000317

AC:

AN:

249062

Hom.:

AF XY:

0.000319

AC XY:

AN XY:

134588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00355

Gnomad SAS exome

AF:

0.000465

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000788

AC:

115

AN:

1459678

Hom.:

Cov.:

AF XY:

0.0000868

AC XY:

AN XY:

726076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00186

Gnomad4 SAS exome

AF:

0.000362

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000144

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000140

ExAC

AF:

0.000264

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MPZL2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.088

T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.072

MetaRNN

Benign

0.0051

T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.23

Sift

Benign

0.35

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0010

B;B

Vest4

0.17

MutPred

0.44

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);

MVP

0.41

MPC

0.067

ClinPred

0.0060

GERP RS

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.023

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000069

dbscSNV1_RF

Benign

0.016

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