rs8788

Positions:

• chr21-33524806-C-A
• chr21-33524806-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000819.5(GART):​c.1261G>T​(p.Val421Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V421I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GART NM_000819.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

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]

GART (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GART	NM_000819.5	c.1261G>T	p.Val421Phe	missense_variant	11/22	ENST00000381815.9	NP_000810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GART	ENST00000381815.9	c.1261G>T	p.Val421Phe	missense_variant	11/22	1	NM_000819.5	ENSP00000371236.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.081
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	.;.;D;D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L;L;L;L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.12	B;B;B;.
Vest4		0.52
MutPred		0.77		Loss of MoRF binding (P = 0.082);Loss of MoRF binding (P = 0.082);Loss of MoRF binding (P = 0.082);Loss of MoRF binding (P = 0.082);
MVP		0.73
MPC		0.28
ClinPred		0.92	D
GERP RS		6.0
Varity_R		0.54
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8788; hg19: chr21-34897113;