17-42954068-T-C

Variant names:

• chr17-42954068-T-C
• rs7218454
• NM_001261434.2:c.954-290A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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]

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AARSD1	NM_001261434.2	c.954-290A>G		intron_variant	Intron 9 of 11	ENST00000427569.7	NP_001248363.1
PTGES3L-AARSD1	NM_001136042.2	c.1476-290A>G		intron_variant	Intron 14 of 16		NP_001129514.2
PTGES3L-AARSD1	NM_025267.4	c.1293-290A>G		intron_variant	Intron 14 of 16		NP_079543.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89687 AN: 152002 Hom.: 29133 Cov.: 33

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.: 3 AF XY: 0.696 AC XY: 89038 AN XY: 127924

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.765

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.856

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.590 AC: 89727 AN: 152120 Hom.: 29148 Cov.: 33 AF XY: 0.593 AC XY: 44120 AN XY: 74390

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.635

Alfa AF: 0.685 Hom.: 30330

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
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs7218454; hg19: chr17-41106085;