NM_207359.3:c.1438A>T

Variant names:

• chr3-30728370-T-A
• NM_207359.3:c.1438A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207359.3(GADL1):​c.1438A>T​(p.Met480Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GADL1 NM_207359.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.1438A>T	p.Met480Leu	missense	Exon 15 of 15	NP_997242.2	Q6ZQY3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADL1	ENST00000282538.10	TSL:5 MANE Select	c.1438A>T	p.Met480Leu	missense	Exon 15 of 15	ENSP00000282538.5	Q6ZQY3-1
	GADL1	ENST00000944950.1		c.1303A>T	p.Met435Leu	missense	Exon 13 of 13	ENSP00000615009.1
	GADL1	ENST00000944949.1		c.1039A>T	p.Met347Leu	missense	Exon 10 of 10	ENSP00000615008.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461556 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111812

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.070	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.21
Sift	Benign	0.098	T
Sift4G	Benign	0.21	T
Polyphen		0.023	B
Vest4		0.62
MutPred		0.76		Gain of loop (P = 0.0312)
MVP		0.048
MPC		0.059
ClinPred		0.90	D
GERP RS		6.0
Varity_R		0.39
gMVP		0.65
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

hg19: chr3-30769862;