rs12757250

Variant names:

• chr1-167770118-T-C
• rs12757250
• NM_003953.6:c.259-2157T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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.

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.259-2157T>C		intron	N/A	NP_003944.1	A8K5D4
	MPZL1	NM_024569.5		c.259-2157T>C		intron	N/A	NP_078845.3
	MPZL1	NM_001146191.2		c.258+4369T>C		intron	N/A	NP_001139663.1	O95297-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL1	ENST00000359523.7	TSL:1 MANE Select	c.259-2157T>C		intron	N/A	ENSP00000352513.2	O95297-1
	MPZL1	ENST00000474859.5	TSL:1	c.259-2157T>C		intron	N/A	ENSP00000420455.1	O95297-3
	MPZL1	ENST00000367853.3	TSL:1	c.181-2157T>C		intron	N/A	ENSP00000356827.3	Q9UEL6

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

African (AFR) AF: 0.0122 AC: 505 AN: 41530

American (AMR) AF: 0.0628 AC: 960 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0187 AC: 90 AN: 4818

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10604

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0715 AC: 4861 AN: 67994

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0548 Hom.: 291

Bravo AF: 0.0495

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.79
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12757250; hg19: chr1-167739355;