rs12065184

Positions:

• chr1-161308887-A-C
• chr1-161308887-A-T

Variant summary

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

The NM_000530.8(MPZ):​c.67+952T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,122 control chromosomes in the GnomAD database, including 547 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 0.080 (547 hom., cov: 31)
• Consequence: MPZ NM_000530.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.985

Genes affected

MPZ (HGNC:7225): (myelin protein zero) This gene is specifically expressed in Schwann cells of the peripheral nervous system and encodes a type I transmembrane glycoprotein that is a major structural protein of the peripheral myelin sheath. The encoded protein contains a large hydrophobic extracellular domain and a smaller basic intracellular domain, which are essential for the formation and stabilization of the multilamellar structure of the compact myelin. Mutations in this gene are associated with autosomal dominant form of Charcot-Marie-Tooth disease type 1 (CMT1B) and other polyneuropathies, such as Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN). A recent study showed that two isoforms are produced from the same mRNA by use of alternative in-frame translation termination codons via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZ	NM_000530.8	c.67+952T>G		intron_variant		ENST00000533357.5	NP_000521.2
MPZ	NM_001315491.2	c.67+952T>G		intron_variant			NP_001302420.1
MPZ	XM_017001321.3	c.97+952T>G		intron_variant			XP_016856810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPZ	ENST00000533357.5	c.67+952T>G		intron_variant		1	NM_000530.8	ENSP00000432943	P1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12123 AN: 152004 Hom.: 547 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0798 AC: 12135 AN: 152122 Hom.: 547 Cov.: 31 AF XY: 0.0805 AC XY: 5985 AN XY: 74360

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0839

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0609

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0622 Hom.: 265

Bravo AF: 0.0832

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.8
DANN	Benign	0.84

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: rs12065184; hg19: chr1-161278677;