Variant chr11-118235578-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_198275.3(MPZL3):c.463A>G(p.Met155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,613,760 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0076 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 12 hom. )

Consequence

MPZL3
NM_198275.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

MPZL3 (HGNC:27279): (myelin protein zero like 3) Predicted to be involved in cell adhesion. Predicted to act upstream of or within extracellular matrix organization and hair cycle. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MPZL3 links:

MPZL3 (HGNC:):

MPZL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00794217).

BP6

Variant 11-118235578-T-C is Benign according to our data. Variant chr11-118235578-T-C is described in ClinVar as [Benign]. Clinvar id is 714056.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00761 (1159/152250) while in subpopulation AFR AF= 0.027 (1120/41528). AF 95% confidence interval is 0.0257. There are 15 homozygotes in gnomad4. There are 549 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZL3	NM_198275.3 linkuse as main transcript	c.463A>G	p.Met155Val	missense_variant	4/6	ENST00000278949.9	NP_938016.1	Q6UWV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MPZL3	ENST00000278949.9 linkuse as main transcript	c.463A>G	p.Met155Val	missense_variant	4/6	1	NM_198275.3	ENSP00000278949.4	Q6UWV2-1
MPZL3	ENST00000527472.1 linkuse as main transcript	c.427A>G	p.Met143Val	missense_variant	4/6	1		ENSP00000432106.1	Q6UWV2-2
MPZL3	ENST00000525386.5 linkuse as main transcript	c.74-2055A>G		intron_variant		1		ENSP00000434636.1	E9PPB1
MPZL3	ENST00000446386.2 linkuse as main transcript	n.252A>G		non_coding_transcript_exon_variant	3/5	2		ENSP00000393594.2	Q6UWV2-3

Frequencies

GnomAD3 genomes

AF:

0.00761

AC:

1157

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

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:

0.0000588

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00190

AC:

476

AN:

250340

Hom.:

AF XY:

0.00150

AC XY:

203

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.0270

Gnomad AMR exome

AF:

0.000928

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000807

AC:

1179

AN:

1461510

Hom.:

Cov.:

AF XY:

0.000717

AC XY:

521

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.0298

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00761

AC:

1159

AN:

152250

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

549

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0270

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00898

ESP6500AA

AF:

0.0259

AC:

114

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00219

AC:

266

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.099

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0079

T;T

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.9

M;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.45

N;N

REVEL

Uncertain

0.31

Sift

Benign

0.080

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.41

B;.

Vest4

0.31

MVP

0.56

MPC

0.076

ClinPred

0.018

GERP RS

4.7

Varity_R

0.23

gMVP

0.33

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