Genetic Variant ASRGL1:p.Val5Ile (chr11-62337990-G-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_001083926.2(ASRGL1):c.13G>A(p.Val5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,600,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ASRGL1
NM_001083926.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2O:1

Conservation

PhyloP100: -0.917

Publications

1 publications found

Variant links:

Genes affected

ASRGL1 (HGNC:16448): (asparaginase and isoaspartyl peptidase 1) Enables asparaginase activity and beta-aspartyl-peptidase activity. Involved in asparagine catabolic process via L-aspartate. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ASRGL1 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ASRGL1 links:

ENSG00000255118 (HGNC:):

ENSG00000255118 links:

Genome browser will be placed here

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=0.02729538).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083926.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASRGL1	NM_001083926.2	MANE Select	c.13G>A	p.Val5Ile	missense	Exon 2 of 7	NP_001077395.1	A0A024R573
ASRGL1	NM_025080.4		c.13G>A	p.Val5Ile	missense	Exon 2 of 7	NP_079356.3
ASRGL1	NM_001441216.1		c.13G>A	p.Val5Ile	missense	Exon 2 of 5	NP_001428145.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASRGL1	ENST00000415229.6	TSL:1 MANE Select	c.13G>A	p.Val5Ile	missense	Exon 2 of 7	ENSP00000400057.2	Q7L266-1
ASRGL1	ENST00000301776.9	TSL:1	c.13G>A	p.Val5Ile	missense	Exon 2 of 7	ENSP00000301776.5	Q7L266-1
ASRGL1	ENST00000628829.2	TSL:1	c.13G>A	p.Val5Ile	missense	Exon 2 of 6	ENSP00000486943.1	E9PJK6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

225088

AF XY:

0.00000820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000994

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000235

AC:

AN:

1447892

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

718896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

42536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25770

East Asian (EAS)

AF:

0.00

AC:

AN:

39278

South Asian (SAS)

AF:

0.00

AC:

AN:

83976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5546

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

1105762

Other (OTH)

AF:

0.0000167

AC:

AN:

59886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

3.1

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.34

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.84

M_CAP

Benign

0.035

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.70

PhyloP100

-0.92

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.030

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

0.88

Polyphen

0.0020

Vest4

0.042

MutPred

0.43

Loss of disorder (P = 0.1656)

MVP

0.33

MPC

0.17

ClinPred

0.059

GERP RS

-4.1

PromoterAI

0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.17

Mutation Taster

=89/11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over