rs7338

Positions:

• chr17-7014384-C-T

Variant summary

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

The ENST00000593646.6(RNASEK):​c.*98C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 1,343,122 control chromosomes in the GnomAD database, including 477,636 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 0.77 (46450 hom., cov: 33)
  • Exomes 𝑓: 0.85 (431186 hom.)
• Consequence: RNASEK ENST00000593646.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160

Genes affected

RNASEK (HGNC:33911): (ribonuclease K) Enables endoribonuclease activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, endonucleolytic. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNASEK-C17orf49 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEK	NM_001004333.5	c.*98C>T		3_prime_UTR_variant	3/3	ENST00000593646.6	NP_001004333.3
RNASEK-C17orf49	NR_037717.1	n.658C>T		non_coding_transcript_exon_variant	3/8
RNASEK	NR_037715.2	n.672C>T		non_coding_transcript_exon_variant	4/4
RNASEK	NR_037716.2	n.451C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEK	ENST00000593646.6	c.*98C>T		3_prime_UTR_variant	3/3	1	NM_001004333.5	ENSP00000468923	P1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117636 AN: 152046 Hom.: 46432 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.800

GnomAD3 exomes AF: 0.808 AC: 134843 AN: 166852 Hom.: 55742 AF XY: 0.826 AC XY: 75850 AN XY: 91854

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.897

Gnomad EAS exome AF: 0.881

Gnomad SAS exome AF: 0.925

Gnomad FIN exome AF: 0.798

Gnomad NFE exome AF: 0.862

Gnomad OTH exome AF: 0.824

GnomAD4 exome AF: 0.848 AC: 1010135 AN: 1190958 Hom.: 431186 Cov.: 15 AF XY: 0.852 AC XY: 507219 AN XY: 595250

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.889

Gnomad4 EAS exome AF: 0.885

Gnomad4 SAS exome AF: 0.922

Gnomad4 FIN exome AF: 0.794

Gnomad4 NFE exome AF: 0.860

Gnomad4 OTH exome AF: 0.845

GnomAD4 genome AF: 0.774 AC: 117699 AN: 152164 Hom.: 46450 Cov.: 33 AF XY: 0.772 AC XY: 57453 AN XY: 74390

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.801

Alfa AF: 0.843 Hom.: 74137

Bravo AF: 0.751

Asia WGS AF: 0.858 AC: 2985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.92
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: rs7338; hg19: chr17-6917703; COSMIC: COSV52351111; COSMIC: COSV52351111;