8-22245559-C-G

Variant names:

• chr8-22245559-C-G
• rs543418485
• NM_001722.3:c.110C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001722.3(POLR3D):​c.110C>G​(p.Pro37Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000206 in 1,262,346 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: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: POLR3D NM_001722.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.94
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07933149).

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.110C>G	p.Pro37Arg	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.110C>G	p.Pro37Arg	missense	Exon 2 of 9	ENSP00000303088.4	P05423
	POLR3D	ENST00000397802.8	TSL:1	c.110C>G	p.Pro37Arg	missense	Exon 1 of 8	ENSP00000380904.3	P05423
	POLR3D	ENST00000861620.1		c.110C>G	p.Pro37Arg	missense	Exon 2 of 9	ENSP00000531679.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000605 AC: 2 AN: 33080 AF XY: 0.0000559

Gnomad AFR exome AF: 0.000641

Gnomad AMR exome AF: 0.000476

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000721 AC: 8 AN: 1110026 Hom.: 0 Cov.: 31 AF XY: 0.00000571 AC XY: 3 AN XY: 525768

African (AFR) AF: 0.000294 AC: 7 AN: 23782

American (AMR) AF: 0.0000953 AC: 1 AN: 10490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14488

East Asian (EAS) AF: 0.00 AC: 0 AN: 27642

South Asian (SAS) AF: 0.00 AC: 0 AN: 21306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4422

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 927646

Other (OTH) AF: 0.00 AC: 0 AN: 44386

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74490

African (AFR) AF: 0.000433 AC: 18 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000598 AC: 6

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	0.67
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.31	B
Vest4		0.54
MutPred		0.33		Gain of MoRF binding (P = 4e-04)
MVP		0.70
MPC		0.40
ClinPred		0.28	T
GERP RS		5.6
PromoterAI		-0.032	Neutral
Varity_R		0.27
gMVP		0.36
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: rs543418485; hg19: chr8-22103072; COSMIC: COSV60570921; COSMIC: COSV60570921;