rs8971

Variant names:

• chr21-33511311-T-C
• rs8971
• NM_000819.5:c.2255A>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.2255A>G​(p.Asp752Gly) variant causes a missense change. The variant allele was found at a frequency of 0.221 in 1,613,908 control chromosomes in the GnomAD database, including 41,671 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (3112 hom., cov: 31)
  • Exomes 𝑓: 0.23 (38559 hom.)
• Consequence: GART NM_000819.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 46 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 (MetaRNN=0.0018827915).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000819.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GART	NM_000819.5	MANE Select	c.2255A>G	p.Asp752Gly	missense	Exon 17 of 22	NP_000810.1	P22102-1
	GART	NM_001136005.1		c.2255A>G	p.Asp752Gly	missense	Exon 17 of 22	NP_001129477.1	P22102-1
	GART	NM_001136006.1		c.2255A>G	p.Asp752Gly	missense	Exon 17 of 22	NP_001129478.1	P22102-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GART	ENST00000381815.9	TSL:1 MANE Select	c.2255A>G	p.Asp752Gly	missense	Exon 17 of 22	ENSP00000371236.4	P22102-1
	GART	ENST00000381831.7	TSL:1	c.2255A>G	p.Asp752Gly	missense	Exon 17 of 22	ENSP00000371253.3	P22102-1
	GART	ENST00000381839.7	TSL:1	c.2255A>G	p.Asp752Gly	missense	Exon 17 of 22	ENSP00000371261.3	P22102-1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27852 AN: 152024 Hom.: 3108 Cov.: 31

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.212 AC: 53377 AN: 251494 AF XY: 0.216

Gnomad AFR exome AF: 0.0477

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.142

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.225 AC: 329422 AN: 1461766 Hom.: 38559 Cov.: 39 AF XY: 0.225 AC XY: 163618 AN XY: 727176

African (AFR) AF: 0.0412 AC: 1378 AN: 33478

American (AMR) AF: 0.220 AC: 9851 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 5032 AN: 26136

East Asian (EAS) AF: 0.140 AC: 5577 AN: 39700

South Asian (SAS) AF: 0.188 AC: 16225 AN: 86254

European-Finnish (FIN) AF: 0.284 AC: 15189 AN: 53414

Middle Eastern (MID) AF: 0.181 AC: 1043 AN: 5768

European-Non Finnish (NFE) AF: 0.236 AC: 262259 AN: 1111898

Other (OTH) AF: 0.213 AC: 12868 AN: 60394

GnomAD4 genome AF: 0.183 AC: 27872 AN: 152142 Hom.: 3112 Cov.: 31 AF XY: 0.188 AC XY: 13948 AN XY: 74374

African (AFR) AF: 0.0516 AC: 2144 AN: 41532

American (AMR) AF: 0.228 AC: 3481 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3468

East Asian (EAS) AF: 0.148 AC: 763 AN: 5164

South Asian (SAS) AF: 0.182 AC: 878 AN: 4824

European-Finnish (FIN) AF: 0.283 AC: 2993 AN: 10580

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.238 AC: 16188 AN: 67986

Other (OTH) AF: 0.211 AC: 445 AN: 2112

Alfa AF: 0.214 Hom.: 13012

Bravo AF: 0.174

TwinsUK AF: 0.218 AC: 809

ALSPAC AF: 0.228 AC: 880

ESP6500AA AF: 0.0601 AC: 265

ESP6500EA AF: 0.232 AC: 1993

ExAC AF: 0.209 AC: 25413

Asia WGS AF: 0.175 AC: 609 AN: 3478

EpiCase AF: 0.238

EpiControl AF: 0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.7
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.065
Sift	Benign	0.31	T
Sift4G	Benign	0.32	T
Polyphen		0.040	B
Vest4		0.34
MPC		0.24
ClinPred		0.027	T
GERP RS		4.4
Varity_R		0.30
gMVP		0.71
Mutation Taster		=85/15	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: rs8971; hg19: chr21-34883618; COSMIC: COSV67818846; COSMIC: COSV67818846;