Variant chr17-15230340-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.66

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
PMP22	NM_000304.4 link	c.*577T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000312280.9	NP_000295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMP22	ENST00000312280 link	c.*577T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_000304.4	ENSP00000308937.3		Q01453

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31038

AN:

151992

Hom.:

4121

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.228

AC XY:

358

AN XY:

1572

show subpopulations

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.:

AF XY:

0.204

AC XY:

15146

AN XY:

74374

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary liability to pressure palsies

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease, type I

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over