X-154399798-C-A

Variant names:

• chrX-154399798-C-A
• rs1286783643
• NM_006013.5:c.191-5C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006013.5(RPL10):​c.191-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,461 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: RPL10 NM_006013.5 splice_region, intron
• Scores: Splicing: ADA: 0.001371
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 0 publications found

Genes affected

RPL10 (HGNC:10298): (ribosomal protein L10) This gene encodes a ribosomal protein that is a component of the 60S ribosome subunit. The related protein in chicken can bind to c-Jun and can repress c-Jun-mediated transcriptional activation. Some studies have detected an association between variation in this gene and autism spectrum disorders, though others do not detect this relationship. There are multiple pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

RPL10 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked, syndromic, 35

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• autism, susceptibility to, X-linked 5

  Inheritance: XL, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006013.5. 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
	RPL10	NM_006013.5	MANE Select	c.191-5C>A		splice_region intron	N/A	NP_006004.3	X5D2T3
	RPL10	NM_001256577.2		c.191-5C>A		splice_region intron	N/A	NP_001243506.2	P27635
	RPL10	NM_001303624.2		c.191-5C>A		splice_region intron	N/A	NP_001290553.1	P27635

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL10	ENST00000369817.7	TSL:5 MANE Select	c.191-5C>A		splice_region intron	N/A	ENSP00000358832.2	P27635
	RPL10	ENST00000344746.8	TSL:1	c.191-5C>A		splice_region intron	N/A	ENSP00000341730.4	P27635
	RPL10	ENST00000458500.5	TSL:1	c.191-5C>A		splice_region intron	N/A	ENSP00000395025.1	A6QRI9

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183447 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097461 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363119

African (AFR) AF: 0.00 AC: 0 AN: 26379

American (AMR) AF: 0.0000284 AC: 1 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54117

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3657

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841952

Other (OTH) AF: 0.00 AC: 0 AN: 46041

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.1
DANN	Benign	0.75
PhyloP100		-0.41
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0014
dbscSNV1_RF	Benign	0.088
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

Other links and lift over

dbSNP: rs1286783643; hg19: chrX-153628139;