17-7014252-G-A

Position:

chr17-7014252-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004333.5(RNASEK):c.263G>A(p.Arg88Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

RNASEK
NM_001004333.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55

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:44419): (RNASEK-C17orf49 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RNASEK (ribonuclease, RNase K) and C17orf49 (chromosome 17 open reading frame 49) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Jan 2011]

RNASEK-C17orf49 links:

RNASEK-C17orf49 (HGNC:):

RNASEK-C17orf49 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1909813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEK	NM_001004333.5 linkuse as main transcript	c.263G>A	p.Arg88Gln	missense_variant	3/3	ENST00000593646.6	NP_001004333.3	Q6P5S7
RNASEK	NR_037715.2 linkuse as main transcript	n.540G>A		non_coding_transcript_exon_variant	4/4
RNASEK	NR_037716.2 linkuse as main transcript	n.319G>A		non_coding_transcript_exon_variant	3/3
RNASEK-C17orf49	NR_037717.1 linkuse as main transcript	n.526G>A		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEK	ENST00000593646.6 linkuse as main transcript	c.263G>A	p.Arg88Gln	missense_variant	3/3	1	NM_001004333.5	ENSP00000468923.2		A0A0C4DH89
RNASEK-C17orf49	ENST00000547302.3 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	2/7	5		ENSP00000450085.1		H0YIS7

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.00

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248136

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.0000653

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461400

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000105

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000198

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

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

May 11, 2022

The c.380G>A (p.R127Q) alteration is located in exon 3 (coding exon 3) of the RNASEK gene. This alteration results from a G to A substitution at nucleotide position 380, causing the arginine (R) at amino acid position 127 to be replaced by a glutamine (Q). 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

0.26

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.061

T;T;.;.;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.91

D;D;.;D;D

M_CAP

Benign

0.0096

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.1

M;.;.;.;.

PROVEAN

Benign

-1.5

N;.;.;.;.

REVEL

Benign

0.18

Sift

Benign

0.13

T;.;.;.;.

Sift4G

Benign

0.073

T;T;T;T;D

Vest4

0.43

MVP

0.055

MPC

1.1

ClinPred

0.57

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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