rs8466

chr16-47354-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016310.5(POLR3K):c.*76T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,543,572 control chromosomes in the GnomAD database, including 22,534 homozygotes. 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: 𝑓 0.20 (3770 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18764 hom.)
• Consequence: POLR3K NM_016310.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

Genes affected

POLR3K (HGNC:14121): (RNA polymerase III subunit K) This gene encodes a small essential subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The carboxy-terminal domain of this subunit shares a high degree of sequence similarity to the carboxy-terminal domain of an RNA polymerase II elongation factor. This similarity in sequence is supported by functional studies showing that this subunit is required for proper pausing and termination during transcription. Pseudogenes of this gene are found on chromosomes 13 and 17.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR3K	NM_016310.5	c.*76T>C		3_prime_UTR_variant	3/3	ENST00000293860.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR3K	ENST00000293860.6	c.*76T>C		3_prime_UTR_variant	3/3	1	NM_016310.5	P1
POLR3K	ENST00000481810.1	n.789T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30311 AN: 152016 Hom.: 3756 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.155 AC: 216221 AN: 1391438 Hom.: 18764 Cov.: 25 AF XY: 0.155 AC XY: 106814 AN XY: 689674

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.000188

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.0924

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.200 AC: 30369 AN: 152134 Hom.: 3770 Cov.: 32 AF XY: 0.194 AC XY: 14435 AN XY: 74400

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0961

Gnomad4 FIN AF: 0.0936

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.220

Alfa AF: 0.174 Hom.: 1236

Bravo AF: 0.212

Asia WGS AF: 0.0670 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.7
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8466; hg19: chr16-97354; COSMIC: COSV53452622;