3-49017259-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.82 (51524 hom., cov: 32)
  • Exomes 𝑓: 0.79 (462194 hom.)
• Consequence: DALRD3 NM_001009996.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0990

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
DALRD3	NM_001009996.3	c.896A>G	p.Gln299Arg	missense_variant	5/12	ENST00000341949.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DALRD3	ENST00000341949.9	c.896A>G	p.Gln299Arg	missense_variant	5/12	1	NM_001009996.3	P2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124692 AN: 152070 Hom.: 51477 Cov.: 32

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

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.: 70 AF XY: 0.796 AC XY: 578700 AN XY: 727236

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.: 32 AF XY: 0.826 AC XY: 61485 AN XY: 74404

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2019

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	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	1.8
Dann	Benign	0.89
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.074	T;T;T;T;T
MetaRNN	Benign	5.8e-7	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.14	N;N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.23	T
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	T
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

Other links and lift over

dbSNP: rs3087866; hg19: chr3-49054692; COSMIC: COSV58246366; COSMIC: COSV58246366;