8-22245499-G-C

Variant names:

• chr8-22245499-G-C
• rs763785352
• NM_001722.3:c.50G>C

Variant summary

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

The NM_001722.3(POLR3D):​c.50G>C​(p.Arg17Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000873 in 1,145,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: POLR3D NM_001722.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57

Genes affected

POLR3D (HGNC:1080): (RNA polymerase III subunit D) This gene complements a temperature-sensitive mutant isolated from the BHK-21 Syrian hamster cell line. It leads to a block in progression through the G1 phase of the cell cycle at nonpermissive temperatures. [provided by RefSeq, Jul 2008]

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=0.20136553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR3D	NM_001722.3	c.50G>C	p.Arg17Pro	missense_variant	Exon 2 of 9	ENST00000306433.9	NP_001713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3D	ENST00000306433.9	c.50G>C	p.Arg17Pro	missense_variant	Exon 2 of 9	1	NM_001722.3	ENSP00000303088.4
POLR3D	ENST00000397802.8	c.50G>C	p.Arg17Pro	missense_variant	Exon 1 of 8	1		ENSP00000380904.3
POLR3D	ENST00000519237.5	c.50G>C	p.Arg17Pro	missense_variant	Exon 2 of 6	3		ENSP00000429677.1
POLR3D	ENST00000518039.1	n.50G>C		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000429821.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000122 AC: 1 AN: 81820 Hom.: 0 AF XY: 0.0000219 AC XY: 1 AN XY: 45638

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000232

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.73e-7 AC: 1 AN: 1145722 Hom.: 0 Cov.: 31 AF XY: 0.00000183 AC XY: 1 AN XY: 547006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000923 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.0076
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.80	.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N;.;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.23	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.067	B;.;B
Vest4		0.66
MutPred		0.32		Gain of glycosylation at R17 (P = 0.0023);Gain of glycosylation at R17 (P = 0.0023);Gain of glycosylation at R17 (P = 0.0023);
MVP		0.53
MPC		0.67
ClinPred		0.85	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.37

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: rs763785352; hg19: chr8-22103012;