chr8-22245499-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001722.3(POLR3D):​c.50G>T​(p.Arg17Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000175 in 1,145,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: POLR3D NM_001722.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18558988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001722.3. 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
	POLR3D	NM_001722.3	MANE Select	c.50G>T	p.Arg17Leu	missense	Exon 2 of 9	NP_001713.2	P05423

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3D	ENST00000306433.9	TSL:1 MANE Select	c.50G>T	p.Arg17Leu	missense	Exon 2 of 9	ENSP00000303088.4	P05423
	POLR3D	ENST00000397802.8	TSL:1	c.50G>T	p.Arg17Leu	missense	Exon 1 of 8	ENSP00000380904.3	P05423
	POLR3D	ENST00000861620.1		c.50G>T	p.Arg17Leu	missense	Exon 2 of 9	ENSP00000531679.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1145722 Hom.: 0 Cov.: 31 AF XY: 0.00000183 AC XY: 1 AN XY: 547006

African (AFR) AF: 0.00 AC: 0 AN: 24638

American (AMR) AF: 0.00 AC: 0 AN: 15934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14980

East Asian (EAS) AF: 0.00 AC: 0 AN: 29974

South Asian (SAS) AF: 0.00 AC: 0 AN: 25252

European-Finnish (FIN) AF: 0.0000263 AC: 1 AN: 38092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3672

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 947588

Other (OTH) AF: 0.00 AC: 0 AN: 45592

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.083
Eigen_PC	Benign	0.081
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.13
Sift	Benign	0.54	T
Sift4G	Benign	0.53	T
Polyphen		0.067	B
Vest4		0.72
MVP		0.61
MPC		0.34
ClinPred		0.52	D
GERP RS		5.6
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.43
Mutation Taster		=73/27	polymorphism

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: rs763785352; hg19: chr8-22103012;