3-30833894-C-A

Variant names:

• chr3-30833894-C-A
• NM_207359.3:c.1009G>T

Variant summary

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

The NM_207359.3(GADL1):​c.1009G>T​(p.Ala337Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GADL1 NM_207359.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADL1	NM_207359.3	c.1009G>T	p.Ala337Ser	missense_variant	Exon 11 of 15	ENST00000282538.10	NP_997242.2
GADL1	XM_017006297.2	c.952G>T	p.Ala318Ser	missense_variant	Exon 11 of 15		XP_016861786.1
GADL1	XM_047448071.1	c.1009G>T	p.Ala337Ser	missense_variant	Exon 11 of 14		XP_047304027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADL1	ENST00000282538.10	c.1009G>T	p.Ala337Ser	missense_variant	Exon 11 of 15	5	NM_207359.3	ENSP00000282538.5
GADL1	ENST00000454381.3	c.1009G>T	p.Ala337Ser	missense_variant	Exon 11 of 12	1		ENSP00000427059.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1009G>T (p.A337S) alteration is located in exon 11 (coding exon 11) of the GADL1 gene. This alteration results from a G to T substitution at nucleotide position 1009, causing the alanine (A) at amino acid position 337 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.53	P;.
Vest4		0.44
MutPred		0.82		Gain of methylation at K333 (P = 0.0688);Gain of methylation at K333 (P = 0.0688);
MVP		0.38
MPC		0.051
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.37
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-30875386;