rs8129605

Variant names:

• chr21-44197995-A-C
• rs8129605
• ENST00000646873.1:c.312-9918A>C

Your query was ambiguous. Multiple possible variants found:

• chr21-44197995-A-C
• chr21-44197995-A-G
• chr21-44197995-A-T

Variant summary

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

The ENST00000646873.1(GATD3):​c.312-9918A>C variant causes a intron 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: 𝑓 0.000043 (0 hom., cov: 13)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GATD3 ENST00000646873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 7 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 (BayesDel_noAF=-1.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATD3	ENST00000646873.1	c.312-9918A>C		intron_variant	Intron 3 of 4			ENSP00000494853.1
GATD3	ENST00000644251.1	c.429-4055A>C		intron_variant	Intron 4 of 4			ENSP00000495305.1
GATD3	ENST00000645487.1	n.*1026A>C		downstream_gene_variant				ENSP00000494347.1

Frequencies

GnomAD3 genomes AF: 0.0000429 AC: 4 AN: 93302 Hom.: 0 Cov.: 13

Gnomad AFR AF: 0.000233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000201

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000429 AC: 4 AN: 93302 Hom.: 0 Cov.: 13 AF XY: 0.0000221 AC XY: 1 AN XY: 45220

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000233 AC: 3 AN: 12896

American (AMR) AF: 0.00 AC: 0 AN: 12094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2710

East Asian (EAS) AF: 0.00 AC: 0 AN: 3960

South Asian (SAS) AF: 0.00 AC: 0 AN: 2722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 222

European-Non Finnish (NFE) AF: 0.0000201 AC: 1 AN: 49692

Other (OTH) AF: 0.00 AC: 0 AN: 1284

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.274 Hom.: 1904

Asia WGS AF: 0.463 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.20
PhyloP100		-1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8129605; hg19: chr21-45617878;