17-7014258-A-G

Position:

chr17-7014258-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004333.5(RNASEK):c.269A>G(p.Asn90Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,613,754 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 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

RNASEK
NM_001004333.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEK	NM_001004333.5 linkuse as main transcript	c.269A>G	p.Asn90Ser	missense_variant	3/3	ENST00000593646.6	NP_001004333.3	Q6P5S7
RNASEK	NR_037715.2 linkuse as main transcript	n.546A>G		non_coding_transcript_exon_variant	4/4
RNASEK	NR_037716.2 linkuse as main transcript	n.325A>G		non_coding_transcript_exon_variant	3/3
RNASEK-C17orf49	NR_037717.1 linkuse as main transcript	n.532A>G		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.269A>G	p.Asn90Ser	missense_variant	3/3	1	NM_001004333.5	ENSP00000468923.2		A0A0C4DH89
RNASEK-C17orf49	ENST00000547302.3 linkuse as main transcript	c.122A>G	p.Asn41Ser	missense_variant	2/7	5		ENSP00000450085.1		H0YIS7

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000157

AC:

AN:

248416

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000590

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

191

AN:

1461500

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000204

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000264

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000166

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

Oct 03, 2022

The c.386A>G (p.N129S) alteration is located in exon 3 (coding exon 3) of the RNASEK gene. This alteration results from a A to G substitution at nucleotide position 386, causing the asparagine (N) at amino acid position 129 to be replaced by a serine (S). 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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T;.;.;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

D;D;.;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.2

M;.;.;.;.

PROVEAN

Pathogenic

-4.6

D;.;.;.;.

REVEL

Uncertain

0.48

Sift

Benign

0.045

D;.;.;.;.

Sift4G

Uncertain

0.049

D;T;D;D;D

Vest4

0.73

MVP

0.17

MPC

0.75

ClinPred

0.73

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.67

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.67

Position offset: -1

DS_DL_spliceai

0.22

Position offset: 19

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