3-49016485-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001009996.3(DALRD3):c.1090G>A(p.Val364Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,614,076 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (12 hom.)
• Consequence: DALRD3 NM_001009996.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.466

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008031756).
• BP6: Variant 3-49016485-C-T is Benign according to our data. Variant chr3-49016485-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3067222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DALRD3	NM_001009996.3	c.1090G>A	p.Val364Ile	missense_variant	8/12	ENST00000341949.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DALRD3	ENST00000341949.9	c.1090G>A	p.Val364Ile	missense_variant	8/12	1	NM_001009996.3	P2

Frequencies

GnomAD3 genomes AF: 0.00192 AC: 292 AN: 152190 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00265 AC: 666 AN: 251082 Hom.: 3 AF XY: 0.00259 AC XY: 351 AN XY: 135716

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00490

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.0170

Gnomad NFE exome AF: 0.00139

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00132 AC: 1924 AN: 1461768 Hom.: 12 Cov.: 36 AF XY: 0.00140 AC XY: 1017 AN XY: 727184

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00514

Gnomad4 SAS exome AF: 0.000858

Gnomad4 FIN exome AF: 0.0182

Gnomad4 NFE exome AF: 0.000543

Gnomad4 OTH exome AF: 0.000994

GnomAD4 genome AF: 0.00192 AC: 292 AN: 152308 Hom.: 5 Cov.: 32 AF XY: 0.00254 AC XY: 189 AN XY: 74470

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00104 Hom.: 1

Bravo AF: 0.000570

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00282 AC: 342

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

DALRD3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	1.9
Dann	Benign	0.57
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.71	T;T;T;T
MetaRNN	Benign	0.0080	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.28	N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.30	T;T;T;T
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.0060	B;B;B;.
Vest4		0.087
MVP		0.20
MPC		0.15
ClinPred		0.010	T
GERP RS		0.38
Varity_R		0.025
gMVP		0.23

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

Other links and lift over

dbSNP: rs145394428; hg19: chr3-49053918;