Variant 3-30839008-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_207359.3(GADL1):c.892C>T(p.Leu298Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,590,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GADL1
NM_207359.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4049524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GADL1	NM_207359.3 linkuse as main transcript	c.892C>T	p.Leu298Phe	missense_variant	9/15	ENST00000282538.10
GADL1	XM_017006297.2 linkuse as main transcript	c.835C>T	p.Leu279Phe	missense_variant	9/15
GADL1	XM_047448071.1 linkuse as main transcript	c.892C>T	p.Leu298Phe	missense_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GADL1	ENST00000282538.10 linkuse as main transcript	c.892C>T	p.Leu298Phe	missense_variant	9/15	5	NM_207359.3	P1	Q6ZQY3-1
GADL1	ENST00000454381.3 linkuse as main transcript	c.892C>T	p.Leu298Phe	missense_variant	9/12	1			Q6ZQY3-3

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000250

AC:

AN:

239688

Hom.:

AF XY:

0.0000231

AC XY:

AN XY:

129658

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000318

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1438176

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

715716

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.0000711

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.11e-7

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2022

The c.892C>T (p.L298F) alteration is located in exon 9 (coding exon 9) of the GADL1 gene. This alteration results from a C to T substitution at nucleotide position 892, causing the leucine (L) at amino acid position 298 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;.

Eigen

Benign

0.028

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.65

N;N

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.6

D;N

REVEL

Benign

0.19

Sift

Benign

0.27

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.11

B;.

Vest4

0.49

MVP

0.14

MPC

0.012

ClinPred

0.13

GERP RS

6.1

Varity_R

0.21

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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