dbSNP rs770474292: DALRD3:p.Gln339His (chr3-49016658-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001009996.3(DALRD3):c.1017G>T(p.Gln339His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DALRD3
NM_001009996.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DALRD3	NM_001009996.3 link	c.1017G>T	p.Gln339His	missense_variant	Exon 7 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.1017G>T	p.Gln339His	missense_variant	Exon 7 of 12	1	NM_001009996.3	ENSP00000344989.4		Q5D0E6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1445898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717344

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1017G>T (p.Q339H) alteration is located in exon 7 (coding exon 7) of the DALRD3 gene. This alteration results from a G to T substitution at nucleotide position 1017, causing the glutamine (Q) at amino acid position 339 to be replaced by a histidine (H). 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

0.48

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

.;T;T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.65

D;D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.1

M;M;.;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.0

D;N;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.68

MutPred

0.39

Gain of disorder (P = 0.0736);Gain of disorder (P = 0.0736);.;.;

MVP

0.83

MPC

0.70

ClinPred

0.98

GERP RS

3.9

Varity_R

0.19

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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