1-167772479-G-T

Variant names:

• chr1-167772479-G-T
• NM_003953.6:c.463G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003953.6(MPZL1):​c.463G>T​(p.Val155Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPZL1 NM_003953.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

Genes affected

MPZL1 (HGNC:7226): (myelin protein zero like 1) Predicted to enable structural molecule activity. Predicted to be involved in cell-cell signaling and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within positive regulation of cell migration. Located in cell surface and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.3171962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPZL1	NM_003953.6	c.463G>T	p.Val155Leu	missense_variant	Exon 3 of 6	ENST00000359523.7	NP_003944.1
MPZL1	NM_024569.5	c.463G>T	p.Val155Leu	missense_variant	Exon 3 of 5		NP_078845.3
MPZL1	XM_047433610.1	c.91G>T	p.Val31Leu	missense_variant	Exon 4 of 7		XP_047289566.1
MPZL1	NM_001146191.2	c.258+6730G>T		intron_variant	Intron 2 of 2		NP_001139663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZL1	ENST00000359523.7	c.463G>T	p.Val155Leu	missense_variant	Exon 3 of 6	1	NM_003953.6	ENSP00000352513.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.072	T;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Uncertain	-0.039	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Uncertain	0.46
Sift	Benign	0.18	T;D;D
Sift4G	Benign	0.18	T;T;T
Polyphen		0.10	B;B;.
Vest4		0.24
MutPred		0.48		Loss of methylation at K157 (P = 0.1436);Loss of methylation at K157 (P = 0.1436);.;
MVP		0.97
MPC		0.42
ClinPred		0.54	D
GERP RS		2.9
Varity_R		0.32
gMVP		0.74

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: chr1-167741716;