1-167787856-G-C

Variant names:

• chr1-167787856-G-C
• NM_003953.6:c.745G>C
• MPZL1 p.Gly249Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003953.6(MPZL1):​c.745G>C​(p.Gly249Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPZL1 NM_003953.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36386985).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003953.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL1	NM_003953.6	MANE Select	c.745G>C	p.Gly249Arg	missense	Exon 6 of 6	NP_003944.1	A8K5D4
	MPZL1	NM_001146191.2		c.295G>C	p.Gly99Arg	missense	Exon 3 of 3	NP_001139663.1	O95297-5
	MPZL1	NM_024569.5		c.*12G>C		3_prime_UTR	Exon 5 of 5	NP_078845.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL1	ENST00000359523.7	TSL:1 MANE Select	c.745G>C	p.Gly249Arg	missense	Exon 6 of 6	ENSP00000352513.2	O95297-1
	MPZL1	ENST00000367853.3	TSL:1	c.*12G>C		3_prime_UTR	Exon 4 of 4	ENSP00000356827.3	Q9UEL6
	MPZL1	ENST00000448405.5	TSL:1	n.*243G>C		non_coding_transcript_exon	Exon 5 of 5	ENSP00000399490.1	F8WFC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.36	T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.90	L
PhyloP100		3.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.38
Mutation Taster		=87/13	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-167757093;