Variant 3-30800968-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207359.3(GADL1):c.1171T>C(p.Phe391Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000638 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

GADL1
NM_207359.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04375145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GADL1	NM_207359.3 linkuse as main transcript	c.1171T>C	p.Phe391Leu	missense_variant	12/15	ENST00000282538.10	NP_997242.2
GADL1	XM_017006297.2 linkuse as main transcript	c.1114T>C	p.Phe372Leu	missense_variant	12/15		XP_016861786.1
GADL1	XM_047448071.1 linkuse as main transcript	c.1171T>C	p.Phe391Leu	missense_variant	12/14		XP_047304027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GADL1	ENST00000282538.10 linkuse as main transcript	c.1171T>C	p.Phe391Leu	missense_variant	12/15	5	NM_207359.3	ENSP00000282538	P1	Q6ZQY3-1
GADL1	ENST00000454381.3 linkuse as main transcript	c.1171T>C	p.Phe391Leu	missense_variant	12/12	1		ENSP00000427059		Q6ZQY3-3

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000756

AC:

AN:

251346

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0000578

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:

0.0000349

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.0000894

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000342

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000582

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

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

Apr 13, 2022

The c.1171T>C (p.F391L) alteration is located in exon 12 (coding exon 12) of the GADL1 gene. This alteration results from a T to C substitution at nucleotide position 1171, causing the phenylalanine (F) at amino acid position 391 to be replaced by a leucine (L). 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

0.00091

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.18

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.17

Sift

Benign

0.41

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0050

B;.

Vest4

0.47

MutPred

0.72

Loss of methylation at K392 (P = 0.0513);Loss of methylation at K392 (P = 0.0513);

MVP

0.040

MPC

0.0098

ClinPred

0.025

GERP RS

5.5

Varity_R

0.17

gMVP

0.52

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