chr3-30800894-T-A

Variant names:

• chr3-30800894-T-A
• rs771004854
• NM_207359.3:c.1245A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_207359.3(GADL1):​c.1245A>T​(p.Leu415Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,916 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GADL1 NM_207359.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.636
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31396767).

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>T	p.Leu415Phe	missense	Exon 12 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.1245A>T	p.Leu415Phe	missense	Exon 12 of 15	ENSP00000282538.5	Q6ZQY3-1
	GADL1	ENST00000454381.3	TSL:1	c.1245A>T	p.Leu415Phe	missense	Exon 12 of 12	ENSP00000427059.1	Q6ZQY3-3
	GADL1	ENST00000944950.1		c.1110A>T	p.Leu370Phe	missense	Exon 10 of 13	ENSP00000615009.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1454916 Hom.: 0 Cov.: 34 AF XY: 0.00000414 AC XY: 3 AN XY: 724256

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5576

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110238

Other (OTH) AF: 0.00 AC: 0 AN: 60258

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

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	0.15
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.64
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.023	D
Sift4G	Benign	0.28	T
Polyphen		0.97	D
Vest4		0.62
MutPred		0.74		Gain of catalytic residue at L415 (P = 0.1306)
MVP		0.18
MPC		0.013
ClinPred		0.77	D
GERP RS		3.1
Varity_R		0.081
gMVP		0.57
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

dbSNP: rs771004854; hg19: chr3-30842386;