NM_003690.5:c.*79G>C

Variant names:

• chr2-178432018-C-G
• rs9678530
• NM_003690.5:c.*79G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003690.5(PRKRA):​c.*79G>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 0.000000757 in 1,320,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 35)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PRKRA NM_003690.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1320388 Hom.: 0 Cov.: 24 AF XY: 0.00000151 AC XY: 1 AN XY: 661506

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000339 AC: 1 AN: 29508

American (AMR) AF: 0.00 AC: 0 AN: 41284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25104

East Asian (EAS) AF: 0.00 AC: 0 AN: 38418

South Asian (SAS) AF: 0.00 AC: 0 AN: 81022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5356

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 992916

Other (OTH) AF: 0.00 AC: 0 AN: 55404

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.51
PhyloP100		-0.34

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: rs9678530; hg19: chr2-179296745;