21-44133763-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_004649.8(GATD3):c.66C>G(p.Ser22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (32 hom., cov: 1)
  • Exomes 𝑓: 0.00061 (89 hom.)
  • Failed GnomAD Quality Control
• Consequence: GATD3 NM_004649.8 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.29

Genes affected

GATD3 (HGNC:1273): (glutamine amidotransferase class 1 domain containing 3) This gene encodes a potential mitochondrial protein that is a member of the DJ-1/PfpI gene family. This protein is overexpressed in fetal Down syndrome brain. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-44133763-C-G is Benign according to our data. Variant chr21-44133763-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2652731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.29 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATD3	NM_004649.8	c.66C>G	p.Ser22=	synonymous_variant	1/7	ENST00000291577.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATD3	ENST00000291577.11	c.66C>G	p.Ser22=	synonymous_variant	1/7	1	NM_004649.8	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 182 AN: 59908 Hom.: 31 Cov.: 1 FAILED QC

Gnomad AFR AF: 0.00634

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000936

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000102

Gnomad OTH AF: 0.00529

GnomAD3 exomes AF: 0.000427 AC: 83 AN: 194408 Hom.: 0 AF XY: 0.000323 AC XY: 34 AN XY: 105190

Gnomad AFR exome AF: 0.00541

Gnomad AMR exome AF: 0.000512

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000684

Gnomad NFE exome AF: 0.0000237

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.000612 AC: 296 AN: 483388 Hom.: 89 Cov.: 0 AF XY: 0.000545 AC XY: 134 AN XY: 245860

Gnomad4 AFR exome AF: 0.00756

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00150

Gnomad4 NFE exome AF: 0.0000371

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00308 AC: 185 AN: 59998 Hom.: 32 Cov.: 1 AF XY: 0.00310 AC XY: 89 AN XY: 28702

Gnomad4 AFR AF: 0.00643

Gnomad4 AMR AF: 0.000935

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00105

Gnomad4 NFE AF: 0.000102

Gnomad4 OTH AF: 0.00515

Alfa AF: 0.000587 Hom.: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

GATD3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.6
Dann	Benign	0.55

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: rs150960051; hg19: chr21-45553645;