Genetic Variant NM_001261434.2:c.1122A>T (chr17-42950710-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001261434.2(AARSD1):c.1122A>T(p.Glu374Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AARSD1
NM_001261434.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.269

Publications

0 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: 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=0.06603536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261434.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AARSD1	NM_001261434.2	MANE Select	c.1122A>T	p.Glu374Asp	missense	Exon 12 of 12	NP_001248363.1	Q9BTE6-1
PTGES3L-AARSD1	NM_001136042.2		c.1644A>T	p.Glu548Asp	missense	Exon 17 of 17	NP_001129514.2	Q9BTE6-3
PTGES3L-AARSD1	NM_025267.4		c.1461A>T	p.Glu487Asp	missense	Exon 17 of 17	NP_079543.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AARSD1	ENST00000427569.7	TSL:5 MANE Select	c.1122A>T	p.Glu374Asp	missense	Exon 12 of 12	ENSP00000400870.1	Q9BTE6-1
PTGES3L-AARSD1	ENST00000421990.7	TSL:2	c.1515A>T	p.Glu505Asp	missense	Exon 17 of 17	ENSP00000409924.2	B3KSP9
PTGES3L-AARSD1	ENST00000409399.6	TSL:5	c.1515A>T	p.Glu505Asp	missense	Exon 18 of 18	ENSP00000386621.2	B3KSP9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0011

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0040

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.27

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

REVEL

Benign

0.062

Sift

Benign

0.32

Sift4G

Benign

0.61

Polyphen

0.0010

Vest4

0.15

MutPred

0.28

Gain of MoRF binding (P = 0.1003)

MVP

0.12

MPC

0.10

ClinPred

0.38

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.056

gMVP

0.43

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over