X-154408969-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006730.4(DNASE1L1):​c.-499G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 248,205 control chromosomes in the GnomAD database, including 7,448 homozygotes. There are 15,078 hemizygotes in GnomAD. 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: 𝑓 0.28 (5886 hom., 8780 hem., cov: 23)
  • Exomes 𝑓: 0.15 (1562 hom. 6298 hem.)
• Consequence: DNASE1L1 NM_006730.4 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: 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006730.4. 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.-88+143G>A		intron	N/A	NP_001290549.1	P49184
	DNASE1L1	NM_006730.4		c.-499G>A		5_prime_UTR	Exon 1 of 8	NP_006721.1	P49184
	DNASE1L1	NM_001009932.3		c.-88+143G>A		intron	N/A	NP_001009932.1	P49184

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L1	ENST00000369808.7	TSL:1	c.-499G>A		5_prime_UTR	Exon 1 of 8	ENSP00000358823.3	P49184
	DNASE1L1	ENST00000369807.6	TSL:1 MANE Select	c.-88+143G>A		intron	N/A	ENSP00000358822.1	P49184
	DNASE1L1	ENST00000309585.9	TSL:1	c.-88+143G>A		intron	N/A	ENSP00000309168.5	P49184

Frequencies

GnomAD3 genomes AF: 0.279 AC: 31056 AN: 111115 Hom.: 5872 Cov.: 23

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.00880

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0763

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.146 AC: 20064 AN: 137038 Hom.: 1562 Cov.: 0 AF XY: 0.148 AC XY: 6298 AN XY: 42660

African (AFR) AF: 0.686 AC: 2556 AN: 3726

American (AMR) AF: 0.202 AC: 1739 AN: 8594

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 205 AN: 3042

East Asian (EAS) AF: 0.0670 AC: 330 AN: 4926

South Asian (SAS) AF: 0.170 AC: 3701 AN: 21783

European-Finnish (FIN) AF: 0.156 AC: 2161 AN: 13895

Middle Eastern (MID) AF: 0.0925 AC: 147 AN: 1589

European-Non Finnish (NFE) AF: 0.113 AC: 8239 AN: 72920

Other (OTH) AF: 0.150 AC: 986 AN: 6563

GnomAD4 genome AF: 0.280 AC: 31122 AN: 111167 Hom.: 5886 Cov.: 23 AF XY: 0.263 AC XY: 8780 AN XY: 33411

African (AFR) AF: 0.688 AC: 20850 AN: 30315

American (AMR) AF: 0.210 AC: 2223 AN: 10592

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 160 AN: 2646

East Asian (EAS) AF: 0.0897 AC: 316 AN: 3522

South Asian (SAS) AF: 0.161 AC: 432 AN: 2689

European-Finnish (FIN) AF: 0.141 AC: 851 AN: 6050

Middle Eastern (MID) AF: 0.0833 AC: 18 AN: 216

European-Non Finnish (NFE) AF: 0.111 AC: 5888 AN: 52940

Other (OTH) AF: 0.250 AC: 378 AN: 1515

Alfa AF: 0.181 Hom.: 7802

Bravo AF: 0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
PhyloP100		0.18
PromoterAI		-0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2070807; hg19: chrX-153637305;