8-22247246-G-T

Variant names:

• chr8-22247246-G-T
• rs1364285740
• NM_001722.3:c.191G>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.191G>T​(p.Ser64Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,258 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: POLR3D NM_001722.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65
• 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=0.2505148).

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.191G>T	p.Ser64Ile	missense	Exon 3 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.191G>T	p.Ser64Ile	missense	Exon 3 of 9	ENSP00000303088.4	P05423
	POLR3D	ENST00000397802.8	TSL:1	c.191G>T	p.Ser64Ile	missense	Exon 2 of 8	ENSP00000380904.3	P05423
	POLR3D	ENST00000861620.1		c.191G>T	p.Ser64Ile	missense	Exon 3 of 9	ENSP00000531679.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251334 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461258 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 726954

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111524

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

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	Pathogenic	0.89
BayesDel_addAF	Benign	-0.0025	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.14
Sift	Uncertain	0.013	D
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.33
MutPred		0.15		Loss of phosphorylation at S64 (P = 0.0098)
MVP		0.56
MPC		0.33
ClinPred		0.67	D
GERP RS		4.5
Varity_R		0.27
gMVP		0.43
Mutation Taster		=69/31	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: rs1364285740; hg19: chr8-22104759;