21-44145591-C-T

Variant names:

• chr21-44145591-C-T
• rs7676
• NM_004649.8:c.*642C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004649.8(GATD3):​c.*642C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: GATD3 NM_004649.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• Publications: 23 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATD3	NM_004649.8	c.*642C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000291577.11	NP_004640.4
GATD3	NR_135220.2	n.1411C>T		non_coding_transcript_exon_variant	Exon 6 of 6
GATD3	NM_198155.5	c.*642C>T		3_prime_UTR_variant	Exon 6 of 6		NP_937798.4
GATD3	XM_017028479.2	c.*642C>T		3_prime_UTR_variant	Exon 6 of 6		XP_016883968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATD3	ENST00000291577.11	c.*642C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_004649.8	ENSP00000291577.6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.796 AC: 119723 AN: 150472 AF XY: 0.791

Gnomad AFR exome AF: 0.667

Gnomad AMR exome AF: 0.798

Gnomad ASJ exome AF: 0.799

Gnomad EAS exome AF: 0.802

Gnomad FIN exome AF: 0.871

Gnomad NFE exome AF: 0.826

Gnomad OTH exome AF: 0.810

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.768 Hom.: 74669

Bravo AF: 0.0115

Asia WGS AF: 0.731 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.045
DANN	Benign	0.49
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7676; hg19: chr21-45565473;