17-7012619-C-T

Position:

• chr17-7012619-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000548577.5(RNASEK):​c.53C>T​(p.Ser18Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNASEK ENST00000548577.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0980

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 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=0.07817641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEK-C17orf49	NR_037717.1	n.203C>T		non_coding_transcript_exon_variant	1/8
RNASEK	NM_001004333.5	c.-65C>T		upstream_gene_variant		ENST00000593646.6	NP_001004333.3
RNASEK	NR_037715.2	n.-5C>T		upstream_gene_variant
RNASEK	NR_037716.2	n.-5C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEK	ENST00000593646.6	c.-65C>T		upstream_gene_variant		1	NM_001004333.5	ENSP00000468923.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444926 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718402

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2023

The c.53C>T (p.S18F) alteration is located in exon 1 (coding exon 1) of the RNASEK gene. This alteration results from a C to T substitution at nucleotide position 53, causing the serine (S) at amino acid position 18 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.018
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MutPred		0.19		Gain of helix (P = 0.0078);
MVP		0.030
MPC		0.41
ClinPred		0.22	T
GERP RS		2.0
Varity_R		0.074
gMVP		0.26

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: rs1909480698; hg19: chr17-6915938;