NM_207359.3:c.1073C>T

Variant names:

• chr3-30801066-G-A
• rs73061102
• NM_207359.3:c.1073C>T

Variant summary

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

The NM_207359.3(GADL1):​c.1073C>T​(p.Ser358Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,220 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S358C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GADL1 NM_207359.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73
• 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.1073C>T	p.Ser358Phe	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.1073C>T	p.Ser358Phe	missense	Exon 12 of 15	ENSP00000282538.5	Q6ZQY3-1
	GADL1	ENST00000454381.3	TSL:1	c.1073C>T	p.Ser358Phe	missense	Exon 12 of 12	ENSP00000427059.1	Q6ZQY3-3
	GADL1	ENST00000944950.1		c.938C>T	p.Ser313Phe	missense	Exon 10 of 13	ENSP00000615009.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461220 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726912

African (AFR) AF: 0.00 AC: 0 AN: 33466

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111634

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.064
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	-0.083	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		3.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.34
Sift	Benign	0.033	D
Sift4G	Uncertain	0.013	D
Polyphen		0.92	P
Vest4		0.77
MutPred		0.65		Gain of helix (P = 0.027)
MVP		0.24
MPC		0.053
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.45
gMVP		0.68
Mutation Taster		=85/15	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: rs73061102; hg19: chr3-30842558;