chrX-154408969-C-A

Variant names:

• chrX-154408969-C-A
• rs2070807
• ENST00000369808.7:c.-499G>T

Variant summary

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

The ENST00000369808.7(DNASE1L1):​c.-499G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: DNASE1L1 ENST00000369808.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• X-linked syndromic intellectual disability

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

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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369808.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L1	NM_001303620.2	MANE Select	c.-88+143G>T		intron	N/A	NP_001290549.1
	DNASE1L1	NM_006730.4		c.-499G>T		5_prime_UTR	Exon 1 of 8	NP_006721.1
	DNASE1L1	NM_001009932.3		c.-88+143G>T		intron	N/A	NP_001009932.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L1	ENST00000369808.7	TSL:1	c.-499G>T		5_prime_UTR	Exon 1 of 8	ENSP00000358823.3
	DNASE1L1	ENST00000369807.6	TSL:1 MANE Select	c.-88+143G>T		intron	N/A	ENSP00000358822.1
	DNASE1L1	ENST00000309585.9	TSL:1	c.-88+143G>T		intron	N/A	ENSP00000309168.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 137168 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 42676

African (AFR) AF: 0.00 AC: 0 AN: 3733

American (AMR) AF: 0.00 AC: 0 AN: 8606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3044

East Asian (EAS) AF: 0.00 AC: 0 AN: 4929

South Asian (SAS) AF: 0.00 AC: 0 AN: 21797

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13919

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1591

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 72977

Other (OTH) AF: 0.00 AC: 0 AN: 6572

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
PhyloP100		0.18
PromoterAI		-0.0084	Neutral

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: rs2070807; hg19: chrX-153637305;