11-118235527-C-T

Position:

chr11-118235527-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198275.3(MPZL3):c.514G>A(p.Val172Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,613,912 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.0058 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 6 hom. )

Consequence

MPZL3
NM_198275.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.590

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008910626).

BP6

Variant 11-118235527-C-T is Benign according to our data. Variant chr11-118235527-C-T is described in ClinVar as [Benign]. Clinvar id is 776663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00584 (888/152164) while in subpopulation AFR AF= 0.0175 (725/41492). AF 95% confidence interval is 0.0164. There are 5 homozygotes in gnomad4. There are 421 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZL3	NM_198275.3 linkuse as main transcript	c.514G>A	p.Val172Met	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.514G>A	p.Val172Met	missense_variant	4/6	1	NM_198275.3	ENSP00000278949.4	Q6UWV2-1
MPZL3	ENST00000527472.1 linkuse as main transcript	c.478G>A	p.Val160Met	missense_variant	4/6	1		ENSP00000432106.1	Q6UWV2-2
MPZL3	ENST00000525386.5 linkuse as main transcript	c.74-2004G>A		intron_variant		1		ENSP00000434636.1	E9PPB1
MPZL3	ENST00000446386.2 linkuse as main transcript	n.303G>A		non_coding_transcript_exon_variant	3/5	2		ENSP00000393594.2	Q6UWV2-3

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

891

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00833

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:

0.000382

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00183

AC:

458

AN:

250950

Hom.:

AF XY:

0.00135

AC XY:

183

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0190

Gnomad AMR exome

AF:

0.00275

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:

0.000335

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.000808

AC:

1181

AN:

1461748

Hom.:

Cov.:

AF XY:

0.000729

AC XY:

530

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000290

Gnomad4 OTH exome

AF:

0.00184

GnomAD4 genome

AF:

0.00584

AC:

888

AN:

152164

Hom.:

Cov.:

AF XY:

0.00566

AC XY:

421

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.00831

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000934

Hom.:

Bravo

AF:

0.00777

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00191

AC:

232

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0089

T;T

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.36

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.90

P;.

Vest4

0.39

MVP

0.46

MPC

0.090

ClinPred

0.019

GERP RS

4.0

Varity_R

0.054

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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