3-49016210-T-A

Variant names:

• chr3-49016210-T-A
• NM_001009996.3:c.1277A>T

Variant summary

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

The NM_001009996.3(DALRD3):​c.1277A>T​(p.Tyr426Phe) 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)
• Consequence: DALRD3 NM_001009996.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

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 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	c.1277A>T	p.Tyr426Phe	missense_variant	Exon 9 of 12	ENST00000341949.9	NP_001009996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DALRD3	ENST00000341949.9	c.1277A>T	p.Tyr426Phe	missense_variant	Exon 9 of 12	1	NM_001009996.3	ENSP00000344989.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1277A>T (p.Y426F) alteration is located in exon 9 (coding exon 9) of the DALRD3 gene. This alteration results from a A to T substitution at nucleotide position 1277, causing the tyrosine (Y) at amino acid position 426 to be replaced by a phenylalanine (F). 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	Benign	0.29
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;T;T;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.9	L;L;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.022	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.65
MutPred		0.40		Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);.;.;
MVP		0.94
MPC		0.69
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.52
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-49053643;