X-103783933-G-GTATATATACATATATTTA

Position:

• chrX-103783933-G-GTATATATACATATATTTA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_000533.5(PLP1):​c.5-1636_5-1619dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.12 (726 hom., 3087 hem., cov: 19)
• Consequence: PLP1 NM_000533.5 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.21

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 Benign. Variant got -9 ACMG points.

• BP6: Variant X-103783933-G-GTATATATACATATATTTA is Benign according to our data. Variant chrX-103783933-G-GTATATATACATATATTTA is described in ClinVar as [Benign]. Clinvar id is 691855.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLP1	NM_000533.5	c.5-1636_5-1619dup		intron_variant		ENST00000621218.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLP1	ENST00000621218.5	c.5-1636_5-1619dup		intron_variant		1	NM_000533.5	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 13236 AN: 110316 Hom.: 727 Cov.: 19 AF XY: 0.0940 AC XY: 3090 AN XY: 32888

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0990

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.000555

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 13228 AN: 110353 Hom.: 726 Cov.: 19 AF XY: 0.0937 AC XY: 3087 AN XY: 32937

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0810

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.000556

Gnomad4 SAS AF: 0.0198

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.122

Alfa AF: 0.130 Hom.: 631

Asia WGS AF: 0.0320 AC: 82 AN: 2519

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:1

Benign, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

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This variant was dentified in a patient with an Xq22del, and noted in the context of the Xq22del mechanism of formation, but not believed to be indepdently causative of the observed phenotype. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs202027037; hg19: chrX-103038862;