chrX-154405018-C-G

Variant names:

• chrX-154405018-C-G
• rs1130929
• NM_001303620.2:c.201G>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001303620.2(DNASE1L1):​c.201G>C​(p.Pro67Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,208,022 control chromosomes in the GnomAD database, including 16,716 homozygotes. There are 57,552 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (5891 hom., 9040 hem., cov: 23)
  • Exomes 𝑓: 0.14 (10825 hom. 48512 hem.)
• Consequence: DNASE1L1 NM_001303620.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.95
• Publications: 13 publications found

Genes affected

DNASE1L1 (HGNC:2957): (deoxyribonuclease 1 like 1) This gene encodes a deoxyribonuclease protein that shows high sequence similarity to DNase I. The encoded protein is localized to the endoplasmic reticulum and modified by N-linked glycosylation. Alternate transcriptional splice variants encoding the same protein have been observed. [provided by RefSeq, Jan 2015]

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, G2P, Labcorp Genetics (formerly Invitae)
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-154405018-C-G is Benign according to our data. Variant chrX-154405018-C-G is described in ClinVar as Benign. ClinVar VariationId is 769188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303620.2. 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
	DNASE1L1	NM_001303620.2	MANE Select	c.201G>C	p.Pro67Pro	synonymous	Exon 3 of 8	NP_001290549.1	P49184
	DNASE1L1	NM_001009932.3		c.201G>C	p.Pro67Pro	synonymous	Exon 5 of 10	NP_001009932.1	P49184
	DNASE1L1	NM_001009933.3		c.201G>C	p.Pro67Pro	synonymous	Exon 4 of 9	NP_001009933.1	P49184

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L1	ENST00000369807.6	TSL:1 MANE Select	c.201G>C	p.Pro67Pro	synonymous	Exon 3 of 8	ENSP00000358822.1	P49184
	DNASE1L1	ENST00000309585.9	TSL:1	c.201G>C	p.Pro67Pro	synonymous	Exon 4 of 9	ENSP00000309168.5	P49184
	DNASE1L1	ENST00000369808.7	TSL:1	c.201G>C	p.Pro67Pro	synonymous	Exon 3 of 8	ENSP00000358823.3	P49184

Frequencies

GnomAD3 genomes AF: 0.281 AC: 31345 AN: 111579 Hom.: 5877 Cov.: 23

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.0604

Gnomad EAS AF: 0.0916

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0720

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.137 AC: 149876 AN: 1096387 Hom.: 10825 Cov.: 32 AF XY: 0.134 AC XY: 48512 AN XY: 361951

African (AFR) AF: 0.716 AC: 18886 AN: 26375

American (AMR) AF: 0.215 AC: 7536 AN: 35056

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 1234 AN: 19323

East Asian (EAS) AF: 0.106 AC: 3200 AN: 30167

South Asian (SAS) AF: 0.169 AC: 9123 AN: 53975

European-Finnish (FIN) AF: 0.150 AC: 6030 AN: 40272

Middle Eastern (MID) AF: 0.0884 AC: 365 AN: 4127

European-Non Finnish (NFE) AF: 0.114 AC: 96206 AN: 841078

Other (OTH) AF: 0.159 AC: 7296 AN: 46014

GnomAD4 genome AF: 0.281 AC: 31420 AN: 111635 Hom.: 5891 Cov.: 23 AF XY: 0.267 AC XY: 9040 AN XY: 33833

African (AFR) AF: 0.689 AC: 21052 AN: 30540

American (AMR) AF: 0.212 AC: 2261 AN: 10674

Ashkenazi Jewish (ASJ) AF: 0.0604 AC: 160 AN: 2647

East Asian (EAS) AF: 0.0910 AC: 320 AN: 3518

South Asian (SAS) AF: 0.163 AC: 444 AN: 2717

European-Finnish (FIN) AF: 0.141 AC: 867 AN: 6128

Middle Eastern (MID) AF: 0.0787 AC: 17 AN: 216

European-Non Finnish (NFE) AF: 0.112 AC: 5911 AN: 52979

Other (OTH) AF: 0.249 AC: 382 AN: 1532

Alfa AF: 0.101 Hom.: 805

Bravo AF: 0.306

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs1130929; hg19: chrX-153633359;