Genetic Variant NM_001009996.3:c.1017G>T (chr3-49016658-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
developmental and epileptic encephalopathy, 86
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae)

DALRD3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009996.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DALRD3	NM_001009996.3	MANE Select	c.1017G>T	p.Gln339His	missense	Exon 7 of 12	NP_001009996.1	Q5D0E6-1
DALRD3	NM_001276405.2		c.1017G>T	p.Gln339His	missense	Exon 7 of 12	NP_001263334.1	Q5D0E6-2
DALRD3	NM_018114.6		c.516G>T	p.Gln172His	missense	Exon 7 of 12	NP_060584.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DALRD3	ENST00000341949.9	TSL:1 MANE Select	c.1017G>T	p.Gln339His	missense	Exon 7 of 12	ENSP00000344989.4	Q5D0E6-1
DALRD3	ENST00000441576.6	TSL:1	c.1017G>T	p.Gln339His	missense	Exon 7 of 12	ENSP00000410623.2	Q5D0E6-2
DALRD3	ENST00000440857.5	TSL:1	c.516G>T	p.Gln172His	missense	Exon 8 of 12	ENSP00000403770.1	C9JJG6

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

African (AFR)

AF:

0.00

AC:

AN:

33228

American (AMR)

AF:

0.00

AC:

AN:

43876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24702

East Asian (EAS)

AF:

0.00

AC:

AN:

39526

South Asian (SAS)

AF:

0.00

AC:

AN:

83822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102668

Other (OTH)

AF:

0.00

AC:

AN:

59700

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.1

PhyloP100

1.0

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.68

MutPred

0.39

Gain of disorder (P = 0.0736)

MVP

0.83

MPC

0.70

ClinPred

0.98

GERP RS

3.9

PromoterAI

0.014

Neutral

(source)

Varity_R

0.19

gMVP

0.61

Mutation Taster

=25/75

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over