Genetic Variant DNASE1L1:p.Asn117Asn (chrX-154403583-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001303620.2(DNASE1L1):c.351C>T(p.Asn117Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,210,390 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 109 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 8 hem., cov: 24)

Exomes 𝑓: 0.00021 ( 0 hom. 101 hem. )

Consequence

DNASE1L1
NM_001303620.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.48

Publications

1 publications found

Variant links:

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]

DNASE1L1 links:

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)

RPL10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-154403583-G-A is Benign according to our data. Variant chrX-154403583-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661803.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.48 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 8 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNASE1L1	NM_001303620.2	MANE Select	c.351C>T	p.Asn117Asn	synonymous	Exon 5 of 8	NP_001290549.1	P49184
DNASE1L1	NM_001009932.3		c.351C>T	p.Asn117Asn	synonymous	Exon 7 of 10	NP_001009932.1	P49184
DNASE1L1	NM_001009933.3		c.351C>T	p.Asn117Asn	synonymous	Exon 6 of 9	NP_001009933.1	P49184

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNASE1L1	ENST00000369807.6	TSL:1 MANE Select	c.351C>T	p.Asn117Asn	synonymous	Exon 5 of 8	ENSP00000358822.1	P49184
DNASE1L1	ENST00000309585.9	TSL:1	c.351C>T	p.Asn117Asn	synonymous	Exon 6 of 9	ENSP00000309168.5	P49184
DNASE1L1	ENST00000369808.7	TSL:1	c.351C>T	p.Asn117Asn	synonymous	Exon 5 of 8	ENSP00000358823.3	P49184

Frequencies

GnomAD3 genomes

AF:

0.000169

AC:

AN:

112276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000943

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00219

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000224

AC:

AN:

183368

AF XY:

0.000265

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000214

AC:

235

AN:

1098061

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

101

AN XY:

363421

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26400

American (AMR)

AF:

0.0000284

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.00137

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40519

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000179

AC:

151

AN:

841976

Other (OTH)

AF:

0.000108

AC:

AN:

46090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000169

AC:

AN:

112329

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

34493

show subpopulations

African (AFR)

AF:

0.000161

AC:

AN:

30965

American (AMR)

AF:

0.0000942

AC:

AN:

10615

Ashkenazi Jewish (ASJ)

AF:

0.000378

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3587

South Asian (SAS)

AF:

0.00220

AC:

AN:

2733

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53188

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000193

EpiCase

AF:

0.000273

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.053

(source)

DANN

Benign

0.84

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over