Variant 17-7012585-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000548577.5(RNASEK):c.19G>A(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000655 in 1,556,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 1 hom. )

Consequence

RNASEK
ENST00000548577.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.789

Variant links:

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 links:

RNASEK-C17orf49 (HGNC:):

RNASEK-C17orf49 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0116533935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
RNASEK-C17orf49	NR_037717.1 linkuse as main transcript	n.169G>A	non_coding_transcript_exon_variant	1/8
RNASEK	NM_001004333.5 linkuse as main transcript	c.-99G>A	upstream_gene_variant		ENST00000593646.6	NP_001004333.3	Q6P5S7
RNASEK	NR_037715.2 linkuse as main transcript	n.-39G>A	upstream_gene_variant
RNASEK	NR_037716.2 linkuse as main transcript	n.-39G>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEK	ENST00000593646.6 linkuse as main transcript	c.-99G>A		upstream_gene_variant		1	NM_001004333.5	ENSP00000468923.2		A0A0C4DH89

Frequencies

GnomAD3 genomes

AF:

0.000591

AC:

AN:

152294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000940

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000473

AC:

AN:

166986

Hom.:

AF XY:

0.000462

AC XY:

AN XY:

90998

show subpopulations

Gnomad AFR exome

AF:

0.000225

Gnomad AMR exome

AF:

0.000453

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000405

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000742

Gnomad OTH exome

AF:

0.000862

GnomAD4 exome

AF:

0.000662

AC:

930

AN:

1404082

Hom.:

Cov.:

AF XY:

0.000665

AC XY:

462

AN XY:

695122

show subpopulations

Gnomad4 AFR exome

AF:

0.000156

Gnomad4 AMR exome

AF:

0.000267

Gnomad4 ASJ exome

AF:

0.000593

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000494

Gnomad4 FIN exome

AF:

0.0000262

Gnomad4 NFE exome

AF:

0.000776

Gnomad4 OTH exome

AF:

0.000751

GnomAD4 genome

AF:

0.000591

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000940

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.000514

ExAC

AF:

0.000229

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

The c.19G>A (p.G7R) alteration is located in exon 1 (coding exon 1) of the RNASEK gene. This alteration results from a G to A substitution at nucleotide position 19, causing the glycine (G) at amino acid position 7 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.4

DANN

Benign

0.91

DEOGEN2

Benign

0.014

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.46

M_CAP

Benign

0.0013

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PROVEAN

Benign

0.19

REVEL

Benign

0.0090

Sift

Benign

0.12

Sift4G

Benign

0.75

Vest4

0.15

MutPred

0.22

Gain of MoRF binding (P = 0.0268);

MVP

0.055

MPC

0.41

ClinPred

0.0053

GERP RS

-5.8

Varity_R

0.044

gMVP

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over