chr16-70271852-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001605.3(AARS1):c.600C>T(p.Ala200Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,613,884 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00090 ( 3 hom. )

Consequence

AARS1
NM_001605.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -2.73

Publications

2 publications found

Variant links:

Genes affected

AARS1 (HGNC:20): (alanyl-tRNA synthetase 1) The human alanyl-tRNA synthetase (AARS) belongs to a family of tRNA synthases, of the class II enzymes. Class II tRNA synthases evolved early in evolution and are highly conserved. This is reflected by the fact that 498 of the 968-residue polypeptide human AARS shares 41% identity witht the E.coli protein. tRNA synthases are the enzymes that interpret the RNA code and attach specific aminoacids to the tRNAs that contain the cognate trinucleotide anticodons. They consist of a catalytic domain which interacts with the amino acid acceptor-T psi C helix of the tRNA, and a second domain which interacts with the rest of the tRNA structure. [provided by RefSeq, Jul 2008]

AARS1 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease axonal type 2N
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
undetermined early-onset epileptic encephalopathy
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Illumina
developmental and epileptic encephalopathy, 29
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
AARS1-related leukoencephalopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
trichothiodystrophy 8, nonphotosensitive
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

AARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-70271852-G-A is Benign according to our data. Variant chr16-70271852-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 197729.

BP7

Synonymous conserved (PhyloP=-2.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000546 (83/152004) while in subpopulation NFE AF = 0.00111 (75/67836). AF 95% confidence interval is 0.000904. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001605.3. 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
	AARS1	NM_001605.3	MANE Select	c.600C>T	p.Ala200Ala	synonymous	Exon 5 of 21	NP_001596.2	P49588-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AARS1	ENST00000261772.13	TSL:1 MANE Select	c.600C>T	p.Ala200Ala	synonymous	Exon 5 of 21	ENSP00000261772.8	P49588-1
AARS1	ENST00000565361.3	TSL:5	c.600C>T	p.Ala200Ala	synonymous	Exon 5 of 22	ENSP00000455360.3	H3BPK7
AARS1	ENST00000896288.1		c.600C>T	p.Ala200Ala	synonymous	Exon 5 of 22	ENSP00000566347.1

Frequencies

GnomAD3 genomes

AF:

0.000546

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00111

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000398

AC:

100

AN:

251482

AF XY:

0.000405

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000765

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000901

AC:

1317

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000851

AC XY:

619

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00111

AC:

1232

AN:

1112006

Other (OTH)

AF:

0.000977

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

149

224

298

373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.000546

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41528

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00111

AC:

AN:

67836

Other (OTH)

AF:

0.000475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000707

Hom.:

Bravo

AF:

0.000518

EpiCase

AF:

0.000545

EpiControl

AF:

0.000711

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Charcot-Marie-Tooth disease axonal type 2N (1)

Charcot-Marie-Tooth disease type 2 (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.4

(source)

DANN

Benign

0.83

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over