3-30778217-T-C

Position:

• chr3-30778217-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207359.3(GADL1):​c.1354A>G​(p.Met452Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,476 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GADL1 NM_207359.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.41

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19323802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GADL1	NM_207359.3	c.1354A>G	p.Met452Val	missense_variant	14/15	ENST00000282538.10	NP_997242.2
GADL1	XM_017006297.2	c.1297A>G	p.Met433Val	missense_variant	14/15		XP_016861786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GADL1	ENST00000282538.10	c.1354A>G	p.Met452Val	missense_variant	14/15	5	NM_207359.3	ENSP00000282538.5
GADL1	ENST00000498387.1	n.411A>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459476 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.1354A>G (p.M452V) alteration is located in exon 14 (coding exon 14) of the GADL1 gene. This alteration results from a A to G substitution at nucleotide position 1354, causing the methionine (M) at amino acid position 452 to be replaced by a valine (V). 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	0.083
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.023
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Benign	0.60	T
Sift4G	Benign	0.23	T
Polyphen		0.079	B
Vest4		0.53
MutPred		0.30		Gain of loop (P = 0.069);
MVP		0.030
MPC		0.010
ClinPred		0.53	D
GERP RS		4.8
Varity_R		0.28
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-30819709;