3-30801066-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/21 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

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 Benign. Variant got -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 id is 2342547.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADL1	NM_207359.3	c.1073C>G	p.Ser358Cys	missense_variant	Exon 12 of 15	ENST00000282538.10	NP_997242.2
GADL1	XM_017006297.2	c.1016C>G	p.Ser339Cys	missense_variant	Exon 12 of 15		XP_016861786.1
GADL1	XM_047448071.1	c.1073C>G	p.Ser358Cys	missense_variant	Exon 12 of 14		XP_047304027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADL1	ENST00000282538.10	c.1073C>G	p.Ser358Cys	missense_variant	Exon 12 of 15	5	NM_207359.3	ENSP00000282538.5
GADL1	ENST00000454381.3	c.1073C>G	p.Ser358Cys	missense_variant	Exon 12 of 12	1		ENSP00000427059.1

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

GnomAD3 exomes AF: 0.000570 AC: 143 AN: 250994 Hom.: 0 AF XY: 0.000582 AC XY: 79 AN XY: 135662

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 SAS 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

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.00154

Gnomad4 OTH exome AF: 0.00111

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

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000569

Gnomad4 NFE AF: 0.00146

Gnomad4 OTH AF: 0.00

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 06, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.022	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.16
Sift	Benign	0.13	T;T
Sift4G	Benign	0.17	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs73061102; hg19: chr3-30842558;