X-103776774-GGAGGAGGAGA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001128834.3(PLP1):c.-143-77_-143-68del variant causes a intron change. The variant allele was found at a frequency of 0.00399 in 419,705 control chromosomes in the GnomAD database, including 20 homozygotes. There are 483 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., 350 hem., cov: 21)
  • Exomes 𝑓: 0.0016 (8 hom. 133 hem.)
• Consequence: PLP1 NM_001128834.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.60

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 -10 ACMG points.

• BP6: Variant X-103776774-GGAGGAGGAGA-G is Benign according to our data. Variant chrX-103776774-GGAGGAGGAGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1202257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1173/107813) while in subpopulation AFR AF= 0.0366 (1086/29698). AF 95% confidence interval is 0.0348. There are 12 homozygotes in gnomad4. There are 350 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLP1	NM_001128834.3	c.-143-77_-143-68del		intron_variant
RAB9B	NR_146558.2	n.433-131_433-122del		intron_variant, non_coding_transcript_variant
RAB9B	NR_146560.2	n.719-131_719-122del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLP1	ENST00000422393.5	c.-143-77_-143-68del		intron_variant		4
PLP1	ENST00000433491.5	c.-143-77_-143-68del		intron_variant		4
PLP1	ENST00000434483.5	c.-143-77_-143-68del		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1167 AN: 107772 Hom.: 12 Cov.: 21 AF XY: 0.0110 AC XY: 343 AN XY: 31092

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00547

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000402

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00446

Gnomad NFE AF: 0.000271

Gnomad OTH AF: 0.0111

GnomAD4 exome AF: 0.00161 AC: 501 AN: 311892 Hom.: 8 AF XY: 0.00137 AC XY: 133 AN XY: 97378

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.00357

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000155

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000197

Gnomad4 OTH exome AF: 0.00568

GnomAD4 genome AF: 0.0109 AC: 1173 AN: 107813 Hom.: 12 Cov.: 21 AF XY: 0.0112 AC XY: 350 AN XY: 31145

Gnomad4 AFR AF: 0.0366

Gnomad4 AMR AF: 0.00547

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000404

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000271

Gnomad4 OTH AF: 0.0110

Alfa AF: 0.00860 Hom.: 20

Bravo AF: 0.0119

Asia WGS AF: 0.00292 AC: 7 AN: 2410

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 13, 2020

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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: rs1377847457; hg19: chrX-103031702;