Genetic Variant DNASE1L1:p.Tyr162Tyr (chrX-154403308-G-A) – ACMG Classification: Benign (-11 pts)

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.Tyr162Tyr) 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.830

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 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
DNASE1L1	NM_001303620.2 link	c.486C>T	p.Tyr162Tyr	synonymous_variant	Exon 6 of 8	ENST00000369807.6	NP_001290549.1	P49184

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE1L1	ENST00000369807.6 link	c.486C>T	p.Tyr162Tyr	synonymous_variant	Exon 6 of 8	1	NM_001303620.2	ENSP00000358822.1		P49184

Frequencies

GnomAD3 genomes

AF:

0.000518

AC:

AN:

111870

Hom.:

Cov.:

AF XY:

0.000499

AC XY:

AN XY:

34050

show subpopulations

Gnomad AFR

AF:

0.0000650

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000164

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000980

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.000453

AC:

AN:

183177

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

67687

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.000251

Gnomad NFE exome

AF:

0.000844

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000459

AC:

504

AN:

1097915

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

181

AN XY:

363355

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.000198

Gnomad4 NFE exome

AF:

0.000556

Gnomad4 OTH exome

AF:

0.000260

GnomAD4 genome

AF:

0.000509

AC:

AN:

111922

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

34112

show subpopulations

Gnomad4 AFR

AF:

0.0000649

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000164

Gnomad4 NFE

AF:

0.000980

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.000872

Hom.:

Bravo

AF:

0.000416

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000544

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNASE1L1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.10

DANN

Benign

0.82

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.28

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.86

PROVEAN

Benign

-0.30

REVEL

Benign

0.026

Sift

Benign

0.45

Sift4G

Benign

0.47

MVP

0.56

ClinPred

0.0076

GERP RS

-4.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over