1-161304965-TTCTC-TTCTCTC

Variant names:

• chr1-161304965-T-TTC
• rs149030537
• NM_000530.8:c.*909_*910dupGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000530.8(MPZ):​c.*909_*910dupGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 149,926 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0031 (0 hom.)
• Consequence: MPZ NM_000530.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPZ	NM_000530.8	c.*909_*910dupGA		3_prime_UTR_variant	Exon 6 of 6	ENST00000533357.5	NP_000521.2
MPZ	NM_001315491.2	c.*717_*718dupGA		3_prime_UTR_variant	Exon 6 of 6		NP_001302420.1
MPZ	XM_017001321.3	c.676-626_676-625dupGA		intron_variant	Intron 5 of 5		XP_016856810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZ	ENST00000533357	c.*909_*910dupGA		3_prime_UTR_variant	Exon 6 of 6	1	NM_000530.8	ENSP00000432943.1

Frequencies

GnomAD3 genomes AF: 0.0000871 AC: 13 AN: 149170 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00314 AC: 2 AN: 636 Hom.: 0 Cov.: 0 AF XY: 0.00263 AC XY: 1 AN XY: 380

Gnomad4 AFR exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0200

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000871 AC: 13 AN: 149290 Hom.: 0 Cov.: 26 AF XY: 0.0000687 AC XY: 5 AN XY: 72736

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149030537; hg19: chr1-161274755;