Genetic Variant NM_080820.6:c.477+14742G>A (chr20-18642975-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080820.6(DTD1):c.477+14742G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,896 control chromosomes in the GnomAD database, including 8,295 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 8207 hom., cov: 30)

Exomes 𝑓: 0.36 ( 88 hom. )

Consequence

DTD1
NM_080820.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Publications

2 publications found

Variant links:

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]

DTD1 links:

ENSG00000284776 (HGNC:):

ENSG00000284776 links:

DUXAP7 (HGNC:32186): (double homeobox A pseudogene 7) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This pseudogene is a member of the DUXA homeobox gene family. [provided by RefSeq, Jul 2008]

DUXAP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTD1	NM_080820.6 link	c.477+14742G>A		intron_variant	Intron 4 of 5	ENST00000377452.4	NP_543010.3	Q8TEA8
DUXAP7		n.18642975G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DTD1	ENST00000377452.4 link	c.477+14742G>A	intron_variant	Intron 4 of 5	1	NM_080820.6	ENSP00000366672.4	Q8TEA8
ENSG00000284776	ENST00000618693.4 link	c.552+14742G>A	intron_variant	Intron 4 of 4	5		ENSP00000482916.1	A0A087WZV9
DUXAP7	ENST00000431038.2 link	n.500-4C>T	splice_region_variant, intron_variant	Intron 1 of 1	6
DTD1	ENST00000647441.1 link	n.*140+14742G>A	intron_variant	Intron 5 of 6			ENSP00000493969.1	A0A2R8YCT7

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47312

AN:

150646

Hom.:

8213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.365

AC:

416

AN:

1140

Hom.:

Cov.:

AF XY:

0.346

AC XY:

233

AN XY:

674

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.292

AC:

AN:

South Asian (SAS)

AF:

0.399

AC:

AN:

138

European-Finnish (FIN)

AF:

0.452

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.367

AC:

299

AN:

814

Other (OTH)

AF:

0.348

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.314

AC:

47313

AN:

150756

Hom.:

8207

Cov.:

AF XY:

0.319

AC XY:

23469

AN XY:

73532

show subpopulations

African (AFR)

AF:

0.170

AC:

6961

AN:

40990

American (AMR)

AF:

0.298

AC:

4511

AN:

15116

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

750

AN:

3462

East Asian (EAS)

AF:

0.422

AC:

2156

AN:

5112

South Asian (SAS)

AF:

0.429

AC:

2050

AN:

4784

European-Finnish (FIN)

AF:

0.423

AC:

4328

AN:

10238

Middle Eastern (MID)

AF:

0.302

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.378

AC:

25605

AN:

67774

Other (OTH)

AF:

0.278

AC:

579

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

1545

3089

4634

6178

7723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.339

Hom.:

1264

Bravo

AF:

0.293

Asia WGS

AF:

0.397

AC:

1377

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.94

(source)

DANN

Benign

0.38

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over