Genetic Variant POLR3K:c.*76T>C (chr16-47354-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.232

Variant links:

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]

POLR3K links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POLR3K	NM_016310.5 link	c.*76T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000293860.6	NP_057394.3	Q9Y2Y1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3K	ENST00000293860 link	c.*76T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_016310.5	ENSP00000293860.5		Q9Y2Y1
POLR3K	ENST00000481810.1 link	n.789T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30311

AN:

152016

Hom.:

3756

Cov.:

show subpopulations

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.:

AF XY:

0.155

AC XY:

106814

AN XY:

689674

show subpopulations

Gnomad4 AFR exome

AF:

0.343

AC:

10821

AN:

31548

Gnomad4 AMR exome

AF:

0.119

AC:

4871

AN:

40838

Gnomad4 ASJ exome

AF:

0.256

AC:

6170

AN:

24134

Gnomad4 EAS exome

AF:

0.000188

AC:

AN:

37154

Gnomad4 SAS exome

AF:

0.111

AC:

9083

AN:

81514

Gnomad4 FIN exome

AF:

0.0924

AC:

4409

AN:

47706

Gnomad4 NFE exome

AF:

0.159

AC:

169814

AN:

1066406

Gnomad4 Remaining exome

AF:

0.171

AC:

9737

AN:

56962

Heterozygous variant carriers

8613

17225

25838

34450

43063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

6124

12248

18372

24496

30620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.200

AC:

30369

AN:

152134

Hom.:

3770

Cov.:

AF XY:

0.194

AC XY:

14435

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.336

AC:

0.33622

AN:

0.33622

Gnomad4 AMR

AF:

0.165

AC:

0.165118

AN:

0.165118

Gnomad4 ASJ

AF:

0.249

AC:

0.24928

AN:

0.24928

Gnomad4 EAS

AF:

0.000771

AC:

0.000771307

AN:

0.000771307

Gnomad4 SAS

AF:

0.0961

AC:

0.096106

AN:

0.096106

Gnomad4 FIN

AF:

0.0936

AC:

0.0935612

AN:

0.0935612

Gnomad4 NFE

AF:

0.159

AC:

0.159304

AN:

0.159304

Gnomad4 OTH

AF:

0.220

AC:

0.22017

AN:

0.22017

Heterozygous variant carriers

1185

2369

3554

4738

5923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.175

Hom.:

1399

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

Mutation Taster

=100/0

polymorphism (auto)

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over