X-103776772-A-AG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001128834.3(PLP1):c.-143-78dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (38093 hom., 32151 hem., cov: 0)
  • Exomes 𝑓: 1.0 (102447 hom. 95179 hem.)
  • Failed GnomAD Quality Control
• Consequence: PLP1 NM_001128834.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.04

Genes affected

PLP1 (HGNC:9086): (proteolipid protein 1) This gene encodes a transmembrane proteolipid protein that is the predominant component of myelin. The encoded protein may play a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. Mutations in this gene cause Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Alternatively splicing results in multiple transcript variants, including the DM20 splice variant. [provided by RefSeq, Feb 2015]

RAB9B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant X-103776772-A-AG is Benign according to our data. Variant chrX-103776772-A-AG is described in ClinVar as [Benign]. Clinvar id is 1238621.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLP1	NM_001128834.3	c.-143-78dup		intron_variant
RAB9B	NR_146558.2	n.433-120_433-119insC		intron_variant, non_coding_transcript_variant
RAB9B	NR_146560.2	n.719-120_719-119insC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLP1	ENST00000422393.5	c.-143-78dup		intron_variant		4
PLP1	ENST00000433491.5	c.-143-78dup		intron_variant		4
PLP1	ENST00000434483.5	c.-143-78dup		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 109097 AN: 109901 Hom.: 38098 Cov.: 0 AF XY: 1.00 AC XY: 32098 AN XY: 32099 FAILED QC

Gnomad AFR AF: 0.975

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.996

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.991

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.998 AC: 300417 AN: 300874 Hom.: 102447 Cov.: 3 AF XY: 0.999 AC XY: 95179 AN XY: 95280

Gnomad4 AFR exome AF: 0.969

Gnomad4 AMR exome AF: 0.996

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.995

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.993 AC: 109140 AN: 109944 Hom.: 38093 Cov.: 0 AF XY: 1.00 AC XY: 32151 AN XY: 32152

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.997

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.991

Alfa AF: 0.991 Hom.: 2809

Asia WGS AF: 0.998 AC: 2512 AN: 2517

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11371342; hg19: chrX-103031700;