Variant chr11-118240258-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198275.3(MPZL3):c.193A>G(p.Thr65Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MPZL3
NM_198275.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

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:

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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=0.35525757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZL3	NM_198275.3 linkuse as main transcript	c.193A>G	p.Thr65Ala	missense_variant	2/6	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.193A>G	p.Thr65Ala	missense_variant	2/6	1	NM_198275.3	ENSP00000278949.4	Q6UWV2-1
MPZL3	ENST00000527472.1 linkuse as main transcript	c.157A>G	p.Thr53Ala	missense_variant	2/6	1		ENSP00000432106.1	Q6UWV2-2
MPZL3	ENST00000525386.5 linkuse as main transcript	c.74-6735A>G		intron_variant		1		ENSP00000434636.1	E9PPB1
MPZL3	ENST00000446386.2 linkuse as main transcript	n.193A>G		non_coding_transcript_exon_variant	2/5	2		ENSP00000393594.2	Q6UWV2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000415

AC:

AN:

240896

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130578

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

May 09, 2023

The c.193A>G (p.T65A) alteration is located in exon 2 (coding exon 2) of the MPZL3 gene. This alteration results from a A to G substitution at nucleotide position 193, causing the threonine (T) at amino acid position 65 to be replaced by an alanine (A). 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

0.29

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.28

Sift

Benign

0.30

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.014

B;.

Vest4

0.50

MutPred

0.49

Loss of phosphorylation at T65 (P = 0.0626);.;

MVP

0.35

MPC

0.073

ClinPred

0.25

GERP RS

5.6

Varity_R

0.077

gMVP

0.54

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