chrX-154403308-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001303620.2(DNASE1L1):c.486C>T(p.Tyr162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000464 in 1,209,837 control chromosomes in the GnomAD database, including 1 homozygotes. There are 198 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 0.00051 ( 0 hom., 17 hem., cov: 24)
Exomes 𝑓: 0.00046 ( 1 hom. 181 hem. )
Consequence
DNASE1L1
NM_001303620.2 synonymous
NM_001303620.2 synonymous
Scores
12
Clinical Significance
Conservation
PhyloP100: -0.830
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.022405297).
BP6
Variant X-154403308-G-A is Benign according to our data. Variant chrX-154403308-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661802.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.83 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 17 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNASE1L1 | NM_001303620.2 | c.486C>T | p.Tyr162= | synonymous_variant | 6/8 | ENST00000369807.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNASE1L1 | ENST00000369807.6 | c.486C>T | p.Tyr162= | synonymous_variant | 6/8 | 1 | NM_001303620.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000518 AC: 58AN: 111870Hom.: 0 Cov.: 24 AF XY: 0.000499 AC XY: 17AN XY: 34050
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GnomAD3 exomes AF: 0.000453 AC: 83AN: 183177Hom.: 0 AF XY: 0.000384 AC XY: 26AN XY: 67687
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GnomAD4 exome AF: 0.000459 AC: 504AN: 1097915Hom.: 1 Cov.: 31 AF XY: 0.000498 AC XY: 181AN XY: 363355
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GnomAD4 genome AF: 0.000509 AC: 57AN: 111922Hom.: 0 Cov.: 24 AF XY: 0.000498 AC XY: 17AN XY: 34112
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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 submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | DNASE1L1: BP4, BP7 - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
MVP
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at