chr21-33537914-T-C

Variant names:

• chr21-33537914-T-C
• rs4817579
• NM_000819.5:c.145+1257A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000819.5(GART):​c.145+1257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,916 control chromosomes in the GnomAD database, including 32,859 homozygotes. 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 0.66 (32859 hom., cov: 30)
• Consequence: GART NM_000819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 11 publications found

Genes affected

GART (HGNC:4163): (phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase) The protein encoded by this gene is a trifunctional polypeptide. It has phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase activity which is required for de novo purine biosynthesis. This enzyme is highly conserved in vertebrates. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GART	NM_000819.5	c.145+1257A>G		intron_variant	Intron 2 of 21	ENST00000381815.9	NP_000810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GART	ENST00000381815.9	c.145+1257A>G		intron_variant	Intron 2 of 21	1	NM_000819.5	ENSP00000371236.4

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99900 AN: 151798 Hom.: 32850 Cov.: 30

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.641

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.658 AC: 99950 AN: 151916 Hom.: 32859 Cov.: 30 AF XY: 0.662 AC XY: 49175 AN XY: 74286

African (AFR) AF: 0.652 AC: 26981 AN: 41408

American (AMR) AF: 0.675 AC: 10299 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1951 AN: 3464

East Asian (EAS) AF: 0.728 AC: 3761 AN: 5164

South Asian (SAS) AF: 0.650 AC: 3131 AN: 4816

European-Finnish (FIN) AF: 0.697 AC: 7353 AN: 10544

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44354 AN: 67946

Other (OTH) AF: 0.635 AC: 1338 AN: 2106

Alfa AF: 0.647 Hom.: 16797

Bravo AF: 0.655

Asia WGS AF: 0.685 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.49
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs4817579; hg19: chr21-34910220;