Variant X-154405502-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001303620.2(DNASE1L1):c.67G>A(p.Ala23Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 1,090,119 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000020 ( 0 hom. 5 hem. )

Consequence

DNASE1L1
NM_001303620.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

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:

DNASE1L1 (HGNC:):

DNASE1L1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE1L1	NM_001303620.2 linkuse as main transcript	c.67G>A	p.Ala23Thr	missense_variant	2/8	ENST00000369807.6	NP_001290549.1	P49184

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNASE1L1	ENST00000369807.6 linkuse as main transcript	c.67G>A	p.Ala23Thr	missense_variant	2/8	1	NM_001303620.2	ENSP00000358822.1		P49184

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000574

AC:

AN:

174325

Hom.:

AF XY:

0.0000166

AC XY:

AN XY:

60203

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000202

AC:

AN:

1090119

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

356515

show subpopulations

Gnomad4 AFR exome

AF:

0.0000762

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000227

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.67G>A (p.A23T) alteration is located in exon 2 (coding exon 1) of the DNASE1L1 gene. This alteration results from a G to A substitution at nucleotide position 67, causing the alanine (A) at amino acid position 23 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

0.0022

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

T;T;T;T;T;T;T;T;.;T;.

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.75

.;T;.;.;.;.;T;T;T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.51

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.2

M;M;M;M;M;M;.;.;.;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.1

N;N;N;N;N;N;D;N;D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.023

D;D;D;D;D;D;D;D;D;T;.

Sift4G

Uncertain

0.059

T;T;T;T;T;T;D;T;.;.;.

Polyphen

1.0

D;D;D;D;D;D;.;.;.;.;.

Vest4

0.26

MutPred

0.62

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.57

MPC

0.92

ClinPred

0.87

GERP RS

2.5

Varity_R

0.31

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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