Genetic Variant AARSD1:c.954-290A>G (chr17-42954068-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001261434.2(AARSD1):c.954-290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 394,820 control chromosomes in the GnomAD database, including 89,112 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 0.59 ( 29148 hom., cov: 33)

Exomes 𝑓: 0.70 ( 59964 hom. )

Consequence

AARSD1
NM_001261434.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.563

Publications

10 publications found

Variant links:

Genes affected

AARSD1 (HGNC:28417): (alanyl-tRNA synthetase domain containing 1) Predicted to enable Ser-tRNA(Ala) hydrolase activity. Predicted to be involved in regulation of translational fidelity. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

AARSD1 links:

PTGES3L-AARSD1 (HGNC:43946): (PTGES3L-AARSD1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring PTGES3L (prostaglandin E synthase 3 (cytosolic)-like) and AARSD1(alanyl-tRNA synthetase domain containing 1) genes on chromosome 17. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, May 2012]

PTGES3L-AARSD1 links:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AARSD1	NM_001261434.2 link	c.954-290A>G	intron_variant	Intron 9 of 11	ENST00000427569.7	NP_001248363.1	Q9BTE6-1
PTGES3L-AARSD1	NM_001136042.2 link	c.1476-290A>G	intron_variant	Intron 14 of 16		NP_001129514.2	Q9BTE6-3
PTGES3L-AARSD1	NM_025267.4 link	c.1293-290A>G	intron_variant	Intron 14 of 16		NP_079543.1	Q9BTE6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AARSD1	ENST00000427569.7 link	c.954-290A>G		intron_variant	Intron 9 of 11	5	NM_001261434.2	ENSP00000400870.1		Q9BTE6-1
PTGES3L-AARSD1	ENST00000421990.7 link	c.1347-290A>G		intron_variant	Intron 14 of 16	2		ENSP00000409924.2		B3KSP9

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89687

AN:

152002

Hom.:

29133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.697

Gnomad AMR

AF:

0.718

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.839

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.637

GnomAD4 exome

AF:

0.696

AC:

168966

AN:

242700

Hom.:

59964

Cov.:

AF XY:

0.696

AC XY:

89038

AN XY:

127924

show subpopulations

African (AFR)

AF:

0.291

AC:

2268

AN:

7796

American (AMR)

AF:

0.765

AC:

9797

AN:

12802

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

4701

AN:

6978

East Asian (EAS)

AF:

0.856

AC:

13009

AN:

15204

South Asian (SAS)

AF:

0.692

AC:

21750

AN:

31434

European-Finnish (FIN)

AF:

0.637

AC:

7893

AN:

12392

Middle Eastern (MID)

AF:

0.665

AC:

666

AN:

1002

European-Non Finnish (NFE)

AF:

0.704

AC:

99550

AN:

141438

Other (OTH)

AF:

0.683

AC:

9332

AN:

13654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2339

4678

7018

9357

11696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.590

AC:

89727

AN:

152120

Hom.:

29148

Cov.:

AF XY:

0.593

AC XY:

44120

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.295

AC:

12260

AN:

41492

American (AMR)

AF:

0.719

AC:

10977

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

2332

AN:

3466

East Asian (EAS)

AF:

0.839

AC:

4343

AN:

5174

South Asian (SAS)

AF:

0.710

AC:

3430

AN:

4830

European-Finnish (FIN)

AF:

0.619

AC:

6546

AN:

10574

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.701

AC:

47686

AN:

67990

Other (OTH)

AF:

0.635

AC:

1342

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1692

3385

5077

6770

8462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.667

Hom.:

37970

Bravo

AF:

0.585

Asia WGS

AF:

0.690

AC:

2399

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.3

(source)

DANN

Benign

0.84

PhyloP100

-0.56

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