rs9901139

Positions:

• chr17-15271991-A-G

Variant summary

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

The ENST00000674868.1(PMP22):​c.-330T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 152,240 control chromosomes in the GnomAD database, including 977 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 0.063 (977 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PMP22 ENST00000674868.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653

Genes affected

PMP22 (HGNC:9118): (peripheral myelin protein 22) This gene encodes an integral membrane protein that is a major component of myelin in the peripheral nervous system. Studies suggest two alternately used promoters drive tissue-specific expression. Various mutations of this gene are causes of Charcot-Marie-Tooth disease Type IA, Dejerine-Sottas syndrome, and hereditary neuropathy with liability to pressure palsies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

PMP22 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.15271991A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMP22	ENST00000674868.1	c.-330T>C		5_prime_UTR_variant	1/5			ENSP00000502835.1
PMP22	ENST00000675350.1	c.-354T>C		5_prime_UTR_variant	1/5			ENSP00000501557.1
PMP22	ENST00000431343.1	n.300T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9537 AN: 152122 Hom.: 976 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.0555

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0629 AC: 9571 AN: 152240 Hom.: 977 Cov.: 33 AF XY: 0.0609 AC XY: 4533 AN XY: 74440

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0411 Hom.: 87

Bravo AF: 0.0712

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9901139; hg19: chr17-15175308;