Genetic Variant PRKRA:c.*79G>A (chr2-178432018-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003690.5(PRKRA):c.*79G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000519 in 1,472,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 35)

Exomes 𝑓: 0.00054 ( 1 hom. )

Consequence

PRKRA
NM_003690.5 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.341

Publications

1 publications found

Variant links:

Genes affected

PRKRA (HGNC:9438): (protein activator of interferon induced protein kinase EIF2AK2) This gene encodes a protein kinase activated by double-stranded RNA which mediates the effects of interferon in response to viral infection. Mutations in this gene have been associated with dystonia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

PRKRA links:

CHROMR (HGNC:54059): (cholesterol induced regulator of metabolism RNA)

CHROMR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003690.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKRA	NM_003690.5	MANE Select	c.*79G>A	3_prime_UTR	Exon 8 of 8	NP_003681.1	O75569-1
PRKRA	NM_001139517.1		c.*79G>A	3_prime_UTR	Exon 7 of 7	NP_001132989.1	O75569-2
PRKRA	NM_001139518.1		c.*79G>A	3_prime_UTR	Exon 8 of 8	NP_001132990.1	O75569-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKRA	ENST00000325748.9	TSL:1 MANE Select	c.*79G>A	3_prime_UTR	Exon 8 of 8	ENSP00000318176.4	O75569-1
PRKRA	ENST00000432031.6	TSL:1	c.*79G>A	3_prime_UTR	Exon 7 of 7	ENSP00000393883.2	O75569-2
PRKRA	ENST00000487082.5	TSL:1	c.*79G>A	3_prime_UTR	Exon 8 of 8	ENSP00000430604.1	O75569-3

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.000456

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000542

AC:

715

AN:

1320276

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

349

AN XY:

661452

show subpopulations

African (AFR)

AF:

0.000136

AC:

AN:

29508

American (AMR)

AF:

0.000339

AC:

AN:

41284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25104

East Asian (EAS)

AF:

0.000130

AC:

AN:

38418

South Asian (SAS)

AF:

0.0000494

AC:

AN:

81022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5356

European-Non Finnish (NFE)

AF:

0.000666

AC:

661

AN:

992808

Other (OTH)

AF:

0.000487

AC:

AN:

55400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.000322

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41578

American (AMR)

AF:

0.000849

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000436

Hom.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dystonia 16 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.61

(source)

DANN

Benign

0.59

PhyloP100

-0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over