11-62338074-G-A

Position:

chr11-62338074-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000415229.6(ASRGL1):c.97G>A(p.Val33Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000901 in 1,607,586 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V33V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0046 ( 10 hom., cov: 34)

Exomes 𝑓: 0.00051 ( 5 hom. )

Consequence

ASRGL1
ENST00000415229.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.278

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010960847).

BP6

Variant 11-62338074-G-A is Benign according to our data. Variant chr11-62338074-G-A is described in ClinVar as [Benign]. Clinvar id is 1170709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00461 (702/152350) while in subpopulation AFR AF= 0.0162 (673/41592). AF 95% confidence interval is 0.0152. There are 10 homozygotes in gnomad4. There are 333 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASRGL1	NM_001083926.2 linkuse as main transcript	c.97G>A	p.Val33Met	missense_variant	2/7	ENST00000415229.6	NP_001077395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASRGL1	ENST00000415229.6 linkuse as main transcript	c.97G>A	p.Val33Met	missense_variant	2/7	1	NM_001083926.2	ENSP00000400057	P1	Q7L266-1
	ENST00000400902.4 linkuse as main transcript	n.17C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.00459

AC:

699

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00115

AC:

272

AN:

235532

Hom.:

AF XY:

0.000883

AC XY:

113

AN XY:

127978

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000942

Gnomad OTH exome

AF:

0.000867

GnomAD4 exome

AF:

0.000513

AC:

746

AN:

1455236

Hom.:

Cov.:

AF XY:

0.000440

AC XY:

318

AN XY:

723394

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.000686

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000470

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000811

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

AF:

0.00461

AC:

702

AN:

152350

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0162

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000816

Hom.:

Bravo

AF:

0.00534

ESP6500AA

AF:

0.0161

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00125

AC:

151

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2023	- -

ASRGL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 17, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

T;T;T;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.65

.;T;T;T;T

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.8

L;L;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.38

N;N;.;.;.

REVEL

Uncertain

0.34

Sift

Benign

0.10

T;T;.;.;.

Sift4G

Benign

0.10

T;T;T;T;T

Polyphen

0.83

P;P;.;.;.

Vest4

0.15

MVP

0.78

MPC

0.24

ClinPred

0.0080

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.18

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over