NM_006013.5:c.236G>C

Variant names:

• chrX-154399848-G-C
• rs782088842
• NM_006013.5:c.236G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006013.5(RPL10):​c.236G>C​(p.Ser79Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,210,574 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: RPL10 NM_006013.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 6.30
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24038762).

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.236G>C	p.Ser79Thr	missense	Exon 5 of 7	NP_006004.3	X5D2T3
	RPL10	NM_001256577.2		c.236G>C	p.Ser79Thr	missense	Exon 5 of 6	NP_001243506.2	P27635
	RPL10	NM_001303624.2		c.236G>C	p.Ser79Thr	missense	Exon 4 of 6	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.236G>C	p.Ser79Thr	missense	Exon 5 of 7	ENSP00000358832.2	P27635
	RPL10	ENST00000344746.8	TSL:1	c.236G>C	p.Ser79Thr	missense	Exon 4 of 6	ENSP00000341730.4	P27635
	RPL10	ENST00000458500.5	TSL:1	c.236G>C	p.Ser79Thr	missense	Exon 5 of 6	ENSP00000395025.1	A6QRI9

Frequencies

GnomAD3 genomes AF: 0.00000889 AC: 1 AN: 112548 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000938

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183481 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098026 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363394

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.0000284 AC: 1 AN: 35206

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842003

Other (OTH) AF: 0.00 AC: 0 AN: 46080

GnomAD4 genome AF: 0.00000889 AC: 1 AN: 112548 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34688

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30932

American (AMR) AF: 0.0000938 AC: 1 AN: 10662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3617

South Asian (SAS) AF: 0.00 AC: 0 AN: 2759

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6183

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53296

Other (OTH) AF: 0.00 AC: 0 AN: 1523

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Intellectual disability, X-linked, syndromic, 35 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.74
DEOGEN2	Benign	0.0015	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.96	T
PhyloP100		6.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.23
Sift	Benign	0.57	T
Sift4G	Benign	0.68	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.37		Loss of MoRF binding (P = 0.1167)
MVP		0.87
MPC		1.5
ClinPred		0.070	T
GERP RS		4.9
PromoterAI		0.0020	Neutral
gMVP		0.82
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs782088842; hg19: chrX-153628189;