21-44175491-G-A

Variant names:

• chr21-44175491-G-A
• rs2838513
• ENST00000411956.1:n.3G>A

Variant summary

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

The ENST00000411956.1(ENSG00000237604):​n.3G>A variant causes a non coding transcript exon 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 0.0014 (1 hom., cov: 10)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000237604 ENST00000411956.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 4 publications found

Genes affected

ENSG00000237604 (HGNC:):

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=-1.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000411956.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000237604	ENST00000411956.1	TSL:3	n.3G>A		non_coding_transcript_exon	Exon 1 of 2
	GATD3	ENST00000646873.1		c.312-32422G>A		intron	N/A	ENSP00000494853.1
	GATD3	ENST00000449622.6	TSL:2	c.490-18133G>A		intron	N/A	ENSP00000400044.2

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 106 AN: 76040 Hom.: 0 Cov.: 10

Gnomad AFR AF: 0.00308

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000583

Gnomad ASJ AF: 0.000585

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000117

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00144 AC: 110 AN: 76144 Hom.: 1 Cov.: 10 AF XY: 0.00148 AC XY: 55 AN XY: 37084

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

African (AFR) AF: 0.00320 AC: 102 AN: 31898

American (AMR) AF: 0.000583 AC: 4 AN: 6866

Ashkenazi Jewish (ASJ) AF: 0.000585 AC: 1 AN: 1708

East Asian (EAS) AF: 0.00 AC: 0 AN: 2196

South Asian (SAS) AF: 0.00 AC: 0 AN: 2684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 160

European-Non Finnish (NFE) AF: 0.000117 AC: 3 AN: 25714

Other (OTH) AF: 0.00 AC: 0 AN: 1002

⚠️ 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: 0.230 Hom.: 1495

Asia WGS AF: 0.606 AC: 2111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.58
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs2838513; hg19: chr21-45595374;