Genetic Variant NM_001303620.2:c.486C>T (chrX-154403308-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.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

Publications

2 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, 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)

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 (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 VariationId 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

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.486C>T	p.Tyr162Tyr	synonymous	Exon 6 of 8	NP_001290549.1	P49184
DNASE1L1	NM_001009932.3		c.486C>T	p.Tyr162Tyr	synonymous	Exon 8 of 10	NP_001009932.1	P49184
DNASE1L1	NM_001009933.3		c.486C>T	p.Tyr162Tyr	synonymous	Exon 7 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.486C>T	p.Tyr162Tyr	synonymous	Exon 6 of 8	ENSP00000358822.1	P49184
DNASE1L1	ENST00000309585.9	TSL:1	c.486C>T	p.Tyr162Tyr	synonymous	Exon 7 of 9	ENSP00000309168.5	P49184
DNASE1L1	ENST00000369808.7	TSL:1	c.486C>T	p.Tyr162Tyr	synonymous	Exon 6 of 8	ENSP00000358823.3	P49184

Frequencies

GnomAD3 genomes

AF:

0.000518

AC:

AN:

111870

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000453

AC:

AN:

183177

AF XY:

0.000384

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 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

African (AFR)

AF:

0.000152

AC:

AN:

26401

American (AMR)

AF:

0.000256

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30200

South Asian (SAS)

AF:

0.0000369

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.000198

AC:

AN:

40335

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.000556

AC:

468

AN:

842022

Other (OTH)

AF:

0.000260

AC:

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000509

AC:

AN:

111922

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

34112

show subpopulations

African (AFR)

AF:

0.0000649

AC:

AN:

30817

American (AMR)

AF:

0.00

AC:

AN:

10592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.00

AC:

AN:

2704

European-Finnish (FIN)

AF:

0.000164

AC:

AN:

6103

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000980

AC:

AN:

53053

Other (OTH)

AF:

0.00131

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000872

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

ClinVar submissions

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

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.10

(source)

DANN

Benign

0.82

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.28

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.86

PhyloP100

-0.83

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

Mutation Taster

=100/0

polymorphism

(source)

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

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