Genetic Variant GADL1:p.Leu415Phe (chr3-30800894-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_207359.3(GADL1):c.1245A>C(p.Leu415Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GADL1
NM_207359.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.636

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28153092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207359.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADL1	NM_207359.3	MANE Select	c.1245A>C	p.Leu415Phe	missense	Exon 12 of 15	NP_997242.2	Q6ZQY3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GADL1	ENST00000282538.10	TSL:5 MANE Select	c.1245A>C	p.Leu415Phe	missense	Exon 12 of 15	ENSP00000282538.5	Q6ZQY3-1
GADL1	ENST00000454381.3	TSL:1	c.1245A>C	p.Leu415Phe	missense	Exon 12 of 12	ENSP00000427059.1	Q6ZQY3-3
GADL1	ENST00000944950.1		c.1110A>C	p.Leu370Phe	missense	Exon 10 of 13	ENSP00000615009.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

247268

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1454912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724256

African (AFR)

AF:

0.00

AC:

AN:

33420

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110238

Other (OTH)

AF:

0.00

AC:

AN:

60258

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.018

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.51

MutationAssessor

Pathogenic

2.9

PhyloP100

0.64

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.36

Sift

Uncertain

0.023

Sift4G

Benign

0.28

Polyphen

0.97

Vest4

0.62

MutPred

0.74

Gain of catalytic residue at L415 (P = 0.1306)

MVP

0.18

MPC

0.013

ClinPred

0.77

GERP RS

3.1

Varity_R

0.081

gMVP

0.57

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over