rs12065184

Variant names:

• chr1-161308887-A-C
• rs12065184
• NM_000530.8:c.67+952T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

MPZ Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 1B

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet
• neuropathy, congenital hypomyelinating, 2

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Charcot-Marie-Tooth disease dominant intermediate D

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Charcot-Marie-Tooth disease type 2I

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Charcot-Marie-Tooth disease type 2J

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Charcot-Marie-Tooth disease type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MPZ	NM_000530.8	c.67+952T>G		intron_variant	Intron 1 of 5	ENST00000533357.5	NP_000521.2
MPZ	NM_001315491.2	c.67+952T>G		intron_variant	Intron 1 of 5		NP_001302420.1
MPZ	XM_017001321.3	c.97+952T>G		intron_variant	Intron 1 of 5		XP_016856810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZ	ENST00000533357.5	c.67+952T>G		intron_variant	Intron 1 of 5	1	NM_000530.8	ENSP00000432943.1
MPZ	ENST00000463290.5	n.67+952T>G		intron_variant	Intron 1 of 6	1		ENSP00000431538.1
MPZ	ENST00000672602.2	c.67+952T>G		intron_variant	Intron 1 of 5			ENSP00000500814.2
MPZ	ENST00000526189.3	c.67+952T>G		intron_variant	Intron 1 of 5	3		ENSP00000488104.2

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

African (AFR) AF: 0.103 AC: 4258 AN: 41464

American (AMR) AF: 0.0839 AC: 1283 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3470

East Asian (EAS) AF: 0.131 AC: 678 AN: 5166

South Asian (SAS) AF: 0.160 AC: 774 AN: 4824

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10594

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0609 AC: 4144 AN: 68006

Other (OTH) AF: 0.101 AC: 212 AN: 2108

Alfa AF: 0.0647 Hom.: 798

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
PhyloP100		0.98
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: rs12065184; hg19: chr1-161278677;