20-18596181-G-A

Variant names:

• chr20-18596181-G-A
• rs776645097
• NM_080820.6:c.310G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080820.6(DTD1):​c.310G>A​(p.Gly104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G104C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTD1 NM_080820.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 1 publications found

Genes affected

DTD1 (HGNC:16219): (D-aminoacyl-tRNA deacylase 1) The protein encoded by this gene is similar in sequence to histidyl-tRNA synthetase, which hydrolyzes D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr). The encoded protein binds the DNA unwinding element and plays a role in the initiation of DNA replication. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ENSG00000284776 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039840937).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080820.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTD1	NM_080820.6	MANE Select	c.310G>A	p.Gly104Ser	missense	Exon 3 of 6	NP_543010.3
	DTD1	NM_001318043.2		c.310G>A	p.Gly104Ser	missense	Exon 3 of 5	NP_001304972.1	A0A2R8Y6X2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTD1	ENST00000377452.4	TSL:1 MANE Select	c.310G>A	p.Gly104Ser	missense	Exon 3 of 6	ENSP00000366672.4	Q8TEA8
	ENSG00000284776	ENST00000618693.4	TSL:5	c.385G>A	p.Gly129Ser	missense	Exon 3 of 5	ENSP00000482916.1	A0A087WZV9
	DTD1	ENST00000916788.1		c.310G>A	p.Gly104Ser	missense	Exon 3 of 7	ENSP00000586847.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N
PhyloP100		0.60
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.10
Sift	Benign	0.72	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.38		Gain of disorder (P = 0.0605)
MVP		0.048
MPC		0.40
ClinPred		0.054	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.11
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs776645097; hg19: chr20-18576825;