17-7014384-C-T

Variant names:

• chr17-7014384-C-T
• rs7338
• ENST00000546395.5:n.*512C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000546395.5(RNASEK):​n.*512C>T variant causes a non coding transcript exon 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 ENST00000546395.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 30 publications found

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: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]

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

C17orf49 (HGNC:28737): (chromosome 17 open reading frame 49) Enables identical protein binding activity. Predicted to be involved in chromatin organization. Located in cytosol and nucleoplasm. Part of MLL1 complex and NURF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNASEK	NM_001004333.5	c.*98C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000593646.6	NP_001004333.3
RNASEK	NR_037715.2	n.672C>T		non_coding_transcript_exon_variant	Exon 4 of 4
RNASEK	NR_037716.2	n.451C>T		non_coding_transcript_exon_variant	Exon 3 of 3
RNASEK-C17orf49	NR_037717.1	n.658C>T		non_coding_transcript_exon_variant	Exon 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEK	ENST00000593646.6	c.*98C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001004333.5	ENSP00000468923.2
RNASEK-C17orf49	ENST00000547302.3	c.141+107C>T		intron_variant	Intron 2 of 6	5		ENSP00000450085.1

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

GnomAD2 exomes AF: 0.808 AC: 134843 AN: 166852 AF XY: 0.826

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 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

African (AFR) AF: 0.614 AC: 16658 AN: 27136

American (AMR) AF: 0.569 AC: 19816 AN: 34824

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 19178 AN: 21564

East Asian (EAS) AF: 0.885 AC: 31968 AN: 36142

South Asian (SAS) AF: 0.922 AC: 68183 AN: 73966

European-Finnish (FIN) AF: 0.794 AC: 34067 AN: 42926

Middle Eastern (MID) AF: 0.895 AC: 3226 AN: 3606

European-Non Finnish (NFE) AF: 0.860 AC: 774188 AN: 900086

Other (OTH) AF: 0.845 AC: 42851 AN: 50708

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

African (AFR) AF: 0.624 AC: 25913 AN: 41502

American (AMR) AF: 0.674 AC: 10306 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3100 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4542 AN: 5158

South Asian (SAS) AF: 0.921 AC: 4441 AN: 4824

European-Finnish (FIN) AF: 0.782 AC: 8288 AN: 10594

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58409 AN: 68004

Other (OTH) AF: 0.801 AC: 1693 AN: 2114

Alfa AF: 0.834 Hom.: 90047

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
PhyloP100		0.16
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7338; hg19: chr17-6917703; COSMIC: COSV52351111; COSMIC: COSV52351111;