Variant 17-15230089-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000304.4(PMP22):c.*828G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 152,626 control chromosomes in the GnomAD database, including 481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 480 hom., cov: 33)

Exomes 𝑓: 0.051 ( 1 hom. )

Consequence

PMP22
NM_000304.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.81

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 17-15230089-C-T is Benign according to our data. Variant chr17-15230089-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 321850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMP22	NM_000304.4 link	c.*828G>A		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.*828G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000304.4	ENSP00000308937.3		Q01453

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9866

AN:

152080

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0182

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.0549

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.0373

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0825

Gnomad OTH

AF:

0.0736

GnomAD4 exome

AF:

0.0514

AC:

AN:

428

Hom.:

Cov.:

AF XY:

0.0508

AC XY:

AN XY:

256

show subpopulations

Gnomad4 FIN exome

AF:

0.0502

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0647

AC:

9854

AN:

152198

Hom.:

480

Cov.:

AF XY:

0.0629

AC XY:

4678

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0182

Gnomad4 AMR

AF:

0.0549

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.0373

Gnomad4 NFE

AF:

0.0825

Gnomad4 OTH

AF:

0.0724

Alfa

AF:

0.0727

Hom.:

106

Bravo

AF:

0.0637

Asia WGS

AF:

0.145

AC:

501

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

-0.35

CADD

Benign

DANN

Benign

0.90

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