Genetic Variant DALRD3:p.Gln299Arg (chr3-49017259-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001009996.3(DALRD3):c.896A>G(p.Gln299Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,614,052 control chromosomes in the GnomAD database, including 513,718 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.82 ( 51524 hom., cov: 32)

Exomes 𝑓: 0.79 ( 462194 hom. )

Consequence

DALRD3
NM_001009996.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0990

Variant links:

Genes affected

DALRD3 (HGNC:25536): (DALR anticodon binding domain containing 3) The exact function of this gene is not known. It encodes a protein with a DALR anticodon binding domain similar to that of class Ia aminoacyl tRNA synthetases. This gene is located in a cluster of genes (with a complex sense-anti-sense genome architecture) on chromosome 3, and contains two micro RNA (miRNA) precursors (mir-425 and mir-191) in one of its introns. Preferential expression of this gene (the miRNAs and other genes in the cluster) in testis suggests a role of this gene in spermatogenesis (PMID:19906709). [provided by RefSeq, Feb 2013]

DALRD3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.7857835E-7).

BP6

Variant 3-49017259-T-C is Benign according to our data. Variant chr3-49017259-T-C is described in ClinVar as [Benign]. Clinvar id is 1232531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DALRD3	NM_001009996.3 link	c.896A>G	p.Gln299Arg	missense_variant	Exon 5 of 12	ENST00000341949.9	NP_001009996.1	Q5D0E6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DALRD3	ENST00000341949.9 link	c.896A>G	p.Gln299Arg	missense_variant	Exon 5 of 12	1	NM_001009996.3	ENSP00000344989.4		Q5D0E6-1

Frequencies

GnomAD3 genomes

AF:

0.820

AC:

124692

AN:

152070

Hom.:

51477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.847

Gnomad ASJ

AF:

0.872

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.808

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.754

Gnomad OTH

AF:

0.806

GnomAD3 exomes

AF:

0.833

AC:

209547

AN:

251478

Hom.:

88362

AF XY:

0.832

AC XY:

113052

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.882

Gnomad AMR exome

AF:

0.902

Gnomad ASJ exome

AF:

0.873

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.939

Gnomad FIN exome

AF:

0.805

Gnomad NFE exome

AF:

0.754

Gnomad OTH exome

AF:

0.808

GnomAD4 exome

AF:

0.792

AC:

1158446

AN:

1461864

Hom.:

462194

Cov.:

AF XY:

0.796

AC XY:

578700

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.886

Gnomad4 AMR exome

AF:

0.895

Gnomad4 ASJ exome

AF:

0.872

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.937

Gnomad4 FIN exome

AF:

0.793

Gnomad4 NFE exome

AF:

0.764

Gnomad4 OTH exome

AF:

0.812

GnomAD4 genome

AF:

0.820

AC:

124799

AN:

152188

Hom.:

51524

Cov.:

AF XY:

0.826

AC XY:

61485

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.883

Gnomad4 AMR

AF:

0.847

Gnomad4 ASJ

AF:

0.872

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.943

Gnomad4 FIN

AF:

0.808

Gnomad4 NFE

AF:

0.754

Gnomad4 OTH

AF:

0.808

Alfa

AF:

0.779

Hom.:

112736

Bravo

AF:

0.826

TwinsUK

AF:

0.770

AC:

2854

ALSPAC

AF:

0.763

AC:

2940

ESP6500AA

AF:

0.877

AC:

3866

ESP6500EA

AF:

0.758

AC:

6518

ExAC

AF:

0.828

AC:

100503

Asia WGS

AF:

0.965

AC:

3355

AN:

3478

EpiCase

AF:

0.757

EpiControl

AF:

0.752

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31178129, 30389748) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.8

DANN

Benign

0.89

DEOGEN2

Benign

0.019

.;T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.074

T;T;T;T;T

MetaRNN

Benign

5.8e-7

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.14

N;N;.;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

0.96

N;N;N;N;N

REVEL

Benign

0.016

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.88

T;T;T;T;.

Polyphen

0.0

B;B;B;.;.

Vest4

0.039

MPC

0.19

ClinPred

0.00071

GERP RS

1.9

Varity_R

0.033

gMVP

0.24

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