X-154405018-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001303620.2(DNASE1L1):c.201G>C(p.Pro67=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNASE1L1	NM_001303620.2	c.201G>C	p.Pro67=	synonymous_variant	3/8	ENST00000369807.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNASE1L1	ENST00000369807.6	c.201G>C	p.Pro67=	synonymous_variant	3/8	1	NM_001303620.2	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 31345 AN: 111579 Hom.: 5877 Cov.: 23 AF XY: 0.266 AC XY: 8991 AN XY: 33767

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

Gnomad4 AFR exome AF: 0.716

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.0639

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.159

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

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.0604

Gnomad4 EAS AF: 0.0910

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.249

Alfa AF: 0.101 Hom.: 805

Bravo AF: 0.306

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 26, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1130929; hg19: chrX-153633359;