10-24937362-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020200.7(PRTFDC1):c.161A>G(p.Glu54Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.37

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRTFDC1	NM_020200.7	c.161A>G	p.Glu54Gly	missense_variant	3/9	ENST00000320152.11
PRTFDC1	NM_001282786.2	c.161A>G	p.Glu54Gly	missense_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRTFDC1	ENST00000320152.11	c.161A>G	p.Glu54Gly	missense_variant	3/9	1	NM_020200.7	P1
PRTFDC1	ENST00000376378.5	c.161A>G	p.Glu54Gly	missense_variant	3/8	2
PRTFDC1	ENST00000376376.3	c.161A>G	p.Glu54Gly	missense_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jul 08, 2022

The c.161A>G (p.E54G) alteration is located in exon 3 (coding exon 3) of the PRTFDC1 gene. This alteration results from a A to G substitution at nucleotide position 161, causing the glutamic acid (E) at amino acid position 54 to be replaced by a glycine (G). 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	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
DEOGEN2	Uncertain	0.73	D;.;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Pathogenic	0.62	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Pathogenic	0.99	D
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-6.0	D;D;D
REVEL	Pathogenic	0.93
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.96	D;D;.
Vest4		0.78
MutPred		0.59		Gain of MoRF binding (P = 0.0834);Gain of MoRF binding (P = 0.0834);Gain of MoRF binding (P = 0.0834);
MVP		0.85
MPC		0.71
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.87
gMVP		0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs982232351; hg19: chr10-25226291;