Variant chr3-30801066-G-C 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_207359.3(GADL1):c.1073C>G(p.Ser358Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00121 in 1,613,132 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

GADL1
NM_207359.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

GADL1 (HGNC:27949): (glutamate decarboxylase like 1) Predicted to enable aspartate 1-decarboxylase activity; pyridoxal phosphate binding activity; and sulfinoalanine decarboxylase activity. Predicted to be involved in carboxylic acid metabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

GADL1 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=0.0219239).

BP6

Variant 3-30801066-G-C is Benign according to our data. Variant chr3-30801066-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2342547.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GADL1	NM_207359.3 linkuse as main transcript	c.1073C>G	p.Ser358Cys	missense_variant	12/15	ENST00000282538.10
GADL1	XM_017006297.2 linkuse as main transcript	c.1016C>G	p.Ser339Cys	missense_variant	12/15
GADL1	XM_047448071.1 linkuse as main transcript	c.1073C>G	p.Ser358Cys	missense_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GADL1	ENST00000282538.10 linkuse as main transcript	c.1073C>G	p.Ser358Cys	missense_variant	12/15	5	NM_207359.3	P1	Q6ZQY3-1
GADL1	ENST00000454381.3 linkuse as main transcript	c.1073C>G	p.Ser358Cys	missense_variant	12/12	1			Q6ZQY3-3

Frequencies

GnomAD3 genomes

AF:

0.000909

AC:

138

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000569

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000570

AC:

143

AN:

250994

Hom.:

AF XY:

0.000582

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000969

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00124

AC:

1812

AN:

1461190

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

854

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000908

AC:

138

AN:

151942

Hom.:

Cov.:

AF XY:

0.000889

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000569

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000916

Hom.:

Bravo

AF:

0.000873

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000445

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.18

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.77

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.16

Sift

Benign

0.13

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.011

B;.

Vest4

0.43

MVP

0.072

MPC

0.011

ClinPred

0.031

GERP RS

4.6

Varity_R

0.19

gMVP

0.54

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