Variant 14-104092711-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080464.3(ASPG):c.161G>A(p.Arg54His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,536,268 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 14 hom. )

Consequence

ASPG
NM_001080464.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

ASPG (HGNC:20123): (asparaginase) Predicted to enable acyltransferase activity, transferring groups other than amino-acyl groups; asparaginase activity; and lysophospholipase activity. Predicted to be involved in asparagine metabolic process and phospholipid metabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ASPG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00717026).

BP6

Variant 14-104092711-G-A is Benign according to our data. Variant chr14-104092711-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 725758.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPG	NM_001080464.3 linkuse as main transcript	c.161G>A	p.Arg54His	missense_variant	2/16	ENST00000551177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPG	ENST00000551177.6 linkuse as main transcript	c.161G>A	p.Arg54His	missense_variant	2/16	1	NM_001080464.3	P1	Q86U10-1
ASPG	ENST00000546892.6 linkuse as main transcript	c.161G>A	p.Arg54His	missense_variant	2/15	1
ASPG	ENST00000548372.5 linkuse as main transcript	n.246G>A		non_coding_transcript_exon_variant	2/11	2

Frequencies

GnomAD3 genomes

AF:

0.000959

AC:

146

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00114

AC:

165

AN:

144940

Hom.:

AF XY:

0.00120

AC XY:

AN XY:

77718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000324

Gnomad ASJ exome

AF:

0.000471

Gnomad EAS exome

AF:

0.00267

Gnomad SAS exome

AF:

0.00215

Gnomad FIN exome

AF:

0.000300

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.00125

AC:

1736

AN:

1383948

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

872

AN XY:

683170

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.000700

Gnomad4 ASJ exome

AF:

0.000478

Gnomad4 EAS exome

AF:

0.00146

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.000279

Gnomad4 NFE exome

AF:

0.00122

Gnomad4 OTH exome

AF:

0.00266

GnomAD4 genome

AF:

0.000965

AC:

147

AN:

152320

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.000899

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000750

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000913

AC:

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.6

DANN

Benign

0.60

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.85

N;N

REVEL

Benign

0.016

Sift

Benign

0.58

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0030

B;B

Vest4

0.067

MVP

0.030

MPC

0.12

ClinPred

0.0023

GERP RS

-3.5

Varity_R

0.016

gMVP

0.47

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