rs12757250

chr1-167770118-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003953.6(MPZL1):c.259-2157T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 152,212 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.048 (251 hom., cov: 32)
• Consequence: MPZL1 NM_003953.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPZL1	NM_003953.6	c.259-2157T>C		intron_variant		ENST00000359523.7
MPZL1	NM_001146191.2	c.258+4369T>C		intron_variant
MPZL1	NM_024569.5	c.259-2157T>C		intron_variant
MPZL1	XM_047433610.1	c.-114-2157T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPZL1	ENST00000359523.7	c.259-2157T>C		intron_variant		1	NM_003953.6	P3

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7360 AN: 152094 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0185

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0589

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0483 AC: 7359 AN: 152212 Hom.: 251 Cov.: 32 AF XY: 0.0466 AC XY: 3468 AN XY: 74430

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0187

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0618 Hom.: 175

Bravo AF: 0.0495

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.99
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs12757250; hg19: chr1-167739355;