chr11-118235562-G-T

Position:

• chr11-118235562-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198275.3(MPZL3):​c.479C>A​(p.Ala160Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPZL3 NM_198275.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.678

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZL3	NM_198275.3	c.479C>A	p.Ala160Asp	missense_variant	4/6	ENST00000278949.9	NP_938016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPZL3	ENST00000278949.9	c.479C>A	p.Ala160Asp	missense_variant	4/6	1	NM_198275.3	ENSP00000278949.4
MPZL3	ENST00000527472.1	c.443C>A	p.Ala148Asp	missense_variant	4/6	1		ENSP00000432106.1
MPZL3	ENST00000525386.5	c.74-2039C>A		intron_variant		1		ENSP00000434636.1
MPZL3	ENST00000446386.2	n.268C>A		non_coding_transcript_exon_variant	3/5	2		ENSP00000393594.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2024

The c.479C>A (p.A160D) alteration is located in exon 4 (coding exon 4) of the MPZL3 gene. This alteration results from a C to A substitution at nucleotide position 479, causing the alanine (A) at amino acid position 160 to be replaced by an aspartic acid (D). 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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.089	T;.
Eigen	Benign	-0.0032
Eigen_PC	Benign	0.048
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.62
Sift	Benign	0.11	T;D
Sift4G	Benign	0.21	T;T
Polyphen		0.81	P;.
Vest4		0.73
MutPred		0.47		Loss of sheet (P = 0.0011);.;
MVP		0.58
MPC		0.19
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.39
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118106277;