rs202027037

Variant names:

• chrX-103783933-G-GTATATATACATATATTTA
• rs202027037
• NM_000533.5:c.5-1636_5-1619dupTATTTATATATATACATA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_000533.5(PLP1):​c.5-1636_5-1619dupTATTTATATATATACATA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 publications found

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]

ENSG00000288597 (HGNC:):

RAB9B (HGNC:14090): (RAB9B, member RAS oncogene family) This gene encodes a member of a subfamily of RAS small guanosine triphosphate (GTP)-binding proteins that regulate membrane trafficking. The encoded protein may be involved in endosome-to-Golgi transport. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000533.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLP1	NM_000533.5	MANE Select	c.5-1636_5-1619dupTATTTATATATATACATA		intron	N/A	NP_000524.3
	PLP1	NM_001128834.3		c.5-1636_5-1619dupTATTTATATATATACATA		intron	N/A	NP_001122306.1	A8K9L3
	PLP1	NM_199478.3		c.5-1636_5-1619dupTATTTATATATATACATA		intron	N/A	NP_955772.1	P60201-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLP1	ENST00000621218.5	TSL:1 MANE Select	c.5-1649_5-1648insTATATATACATATATTTA		intron	N/A	ENSP00000484450.1	P60201-1
	PLP1	ENST00000619236.1	TSL:1	c.5-1649_5-1648insTATATATACATATATTTA		intron	N/A	ENSP00000477619.1	P60201-2
	PLP1	ENST00000867712.1		c.5-1649_5-1648insTATATATACATATATTTA		intron	N/A	ENSP00000537771.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 13236 AN: 110316 Hom.: 727 Cov.: 19

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

African (AFR) AF: 0.145 AC: 4401 AN: 30266

American (AMR) AF: 0.0810 AC: 843 AN: 10402

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 374 AN: 2629

East Asian (EAS) AF: 0.000556 AC: 2 AN: 3594

South Asian (SAS) AF: 0.0198 AC: 54 AN: 2730

European-Finnish (FIN) AF: 0.0763 AC: 427 AN: 5598

Middle Eastern (MID) AF: 0.280 AC: 59 AN: 211

European-Non Finnish (NFE) AF: 0.129 AC: 6816 AN: 52733

Other (OTH) AF: 0.122 AC: 185 AN: 1513

Alfa AF: 0.130 Hom.: 631

Asia WGS AF: 0.0320 AC: 82 AN: 2519

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs202027037; hg19: chrX-103038862;