10-24849851-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020200.7(PRTFDC1):c.671G>A(p.Arg224Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRTFDC1 NM_020200.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.665

Genes affected

PRTFDC1 (HGNC:23333): (phosphoribosyl transferase domain containing 1) Enables protein homodimerization activity. Predicted to be involved in purine ribonucleoside salvage. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13064489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRTFDC1	NM_020200.7	c.671G>A	p.Arg224Gln	missense_variant	9/9	ENST00000320152.11
PRTFDC1	NM_001282786.2	c.*21G>A		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRTFDC1	ENST00000320152.11	c.671G>A	p.Arg224Gln	missense_variant	9/9	1	NM_020200.7	P1
PRTFDC1	ENST00000376378.5	c.*21G>A		3_prime_UTR_variant	8/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.671G>A (p.R224Q) alteration is located in exon 9 (coding exon 9) of the PRTFDC1 gene. This alteration results from a G to A substitution at nucleotide position 671, causing the arginine (R) at amino acid position 224 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.13	T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	0.14	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.30
Sift	Benign	0.17	T
Sift4G	Benign	0.097	T
Polyphen		0.062	B
Vest4		0.14
MutPred		0.25		Loss of methylation at R224 (P = 0.0315);
MVP		0.63
MPC		0.18
ClinPred		0.54	D
GERP RS		2.4
Varity_R		0.17
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs757699463; hg19: chr10-25138780;