17-15230340-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000304.4(PMP22):c.*577T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 155,022 control chromosomes in the GnomAD database, including 4,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (4122 hom., cov: 33)
  • Exomes 𝑓: 0.23 (96 hom.)
• Consequence: PMP22 NM_000304.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.66

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-15230340-A-G is Benign according to our data. Variant chr17-15230340-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 321851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMP22	NM_000304.4	c.*577T>C		3_prime_UTR_variant	5/5	ENST00000312280.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMP22	ENST00000312280.9	c.*577T>C		3_prime_UTR_variant	5/5	1	NM_000304.4	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31038 AN: 151992 Hom.: 4121 Cov.: 33

Gnomad AFR AF: 0.0599

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00907

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.228 AC: 664 AN: 2912 Hom.: 96 Cov.: 0 AF XY: 0.228 AC XY: 358 AN XY: 1572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.204 AC: 31041 AN: 152110 Hom.: 4122 Cov.: 33 AF XY: 0.204 AC XY: 15146 AN XY: 74374

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.00929

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.205

Alfa AF: 0.258 Hom.: 5658

Bravo AF: 0.187

Asia WGS AF: 0.0980 AC: 345 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary liability to pressure palsies Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Charcot-Marie-Tooth disease, type I Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.22
Dann	Benign	0.66

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: rs7538; hg19: chr17-15133657; COSMIC: COSV56602193; COSMIC: COSV56602193;