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X-154403583-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001303620.2(DNASE1L1):c.351C>T(p.Asn117=) 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

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.48
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-154403583-G-A is Benign according to our data. Variant chrX-154403583-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661803.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.48 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNASE1L1NM_001303620.2 linkuse as main transcriptc.351C>T p.Asn117= synonymous_variant 5/8 ENST00000369807.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNASE1L1ENST00000369807.6 linkuse as main transcriptc.351C>T p.Asn117= synonymous_variant 5/81 NM_001303620.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000169
AC:
19
AN:
112276
Hom.:
0
Cov.:
24
AF XY:
0.000232
AC XY:
8
AN XY:
34430
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
GnomAD3 exomes
AF:
0.000224
AC:
41
AN:
183368
Hom.:
0
AF XY:
0.000265
AC XY:
18
AN XY:
67872
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 SAS exome
AF:
0.00136
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.:
0
Cov.:
30
AF XY:
0.000278
AC XY:
101
AN XY:
363421
show subpopulations
Gnomad4 AFR exome
AF:
0.0000758
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.0000516
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00137
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.000179
Gnomad4 OTH exome
AF:
0.000108
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000169
AC:
19
AN:
112329
Hom.:
0
Cov.:
24
AF XY:
0.000232
AC XY:
8
AN XY:
34493
show subpopulations
Gnomad4 AFR
AF:
0.000161
Gnomad4 AMR
AF:
0.0000942
Gnomad4 ASJ
AF:
0.000378
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00220
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000113
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.000193
EpiCase
AF:
0.000273
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023DNASE1L1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
0.053
Dann
Benign
0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373072839; hg19: chrX-153631924; COSMIC: COSV50011052; COSMIC: COSV50011052; API