rs752956051

Variant names:

• chr21-44143322-C-G
• rs752956051
• NM_004649.8:c.639C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-44143322-C-G
• chr21-44143322-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_004649.8(GATD3):​c.639C>G​(p.Ile213Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: GATD3 NM_004649.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31223196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004649.8. 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
	GATD3	NM_004649.8	MANE Select	c.639C>G	p.Ile213Met	missense	Exon 6 of 7	NP_004640.4	P0DPI2-1
	GATD3	NM_198155.5		c.546C>G	p.Ile182Met	missense	Exon 5 of 6	NP_937798.4	P0DPI2-2
	GATD3	NR_135220.2		n.601C>G		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATD3	ENST00000291577.11	TSL:1 MANE Select	c.639C>G	p.Ile213Met	missense	Exon 6 of 7	ENSP00000291577.6	P0DPI2-1
	GATD3	ENST00000348499.9	TSL:1	c.546C>G	p.Ile182Met	missense	Exon 5 of 6	ENSP00000344901.5	P0DPI2-2
	GATD3	ENST00000938560.1		c.636C>G	p.Ile212Met	missense	Exon 6 of 7	ENSP00000608619.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250054 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000531

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.0000301 Hom.: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

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	0.32
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	0.087
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.70	T
PhyloP100		2.4
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.27
Sift	Benign	0.038	D
Sift4G	Uncertain	0.035	D
Vest4		0.64
MVP		0.77
MPC		0.15
ClinPred		0.12	T
GERP RS		2.8
Varity_R		0.17
gMVP		0.76
Mutation Taster		=57/43	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: rs752956051; hg19: chr21-45563204; COSMIC: COSV105107147; COSMIC: COSV105107147;