chr3-30801066-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_207359.3(GADL1):​c.1073C>G​(p.Ser358Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00121 in 1,613,132 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: GADL1 NM_207359.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.73
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0219239).
• BP6: Variant 3-30801066-G-C is Benign according to our data. Variant chr3-30801066-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2342547.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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>G	p.Ser358Cys	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>G	p.Ser358Cys	missense	Exon 12 of 15	ENSP00000282538.5	Q6ZQY3-1
	GADL1	ENST00000454381.3	TSL:1	c.1073C>G	p.Ser358Cys	missense	Exon 12 of 12	ENSP00000427059.1	Q6ZQY3-3
	GADL1	ENST00000944950.1		c.938C>G	p.Ser313Cys	missense	Exon 10 of 13	ENSP00000615009.1

Frequencies

GnomAD3 genomes AF: 0.000909 AC: 138 AN: 151826 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000569

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000570 AC: 143 AN: 250994 AF XY: 0.000582

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000969

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00124 AC: 1812 AN: 1461190 Hom.: 3 Cov.: 34 AF XY: 0.00117 AC XY: 854 AN XY: 726904

African (AFR) AF: 0.000209 AC: 7 AN: 33466

American (AMR) AF: 0.000403 AC: 18 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: 0.0000116 AC: 1 AN: 86204

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53324

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

European-Non Finnish (NFE) AF: 0.00154 AC: 1708 AN: 1111604

Other (OTH) AF: 0.00111 AC: 67 AN: 60358

GnomAD4 genome AF: 0.000908 AC: 138 AN: 151942 Hom.: 0 Cov.: 31 AF XY: 0.000889 AC XY: 66 AN XY: 74260

African (AFR) AF: 0.000289 AC: 12 AN: 41548

American (AMR) AF: 0.00138 AC: 21 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.000569 AC: 6 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 67938

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000916 Hom.: 0

Bravo AF: 0.000873

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.000445 AC: 54

Asia WGS AF: 0.000289 AC: 2 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.80
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.7
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.16
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.011	B
Vest4		0.43
MVP		0.072
MPC		0.011
ClinPred		0.031	T
GERP RS		4.6
Varity_R		0.19
gMVP		0.54
Mutation Taster		=85/15	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

dbSNP: rs73061102; hg19: chr3-30842558;