rs7338

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-7014384-C-G
• chr17-7014384-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000546395.5(RNASEK):​n.*512C>G 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 0.00000252 in 1,192,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: RNASEK ENST00000546395.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEK	NM_001004333.5	c.*98C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000593646.6	NP_001004333.3
RNASEK	NR_037715.2	n.672C>G		non_coding_transcript_exon_variant	Exon 4 of 4
RNASEK	NR_037716.2	n.451C>G		non_coding_transcript_exon_variant	Exon 3 of 3
RNASEK-C17orf49	NR_037717.1	n.658C>G		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>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_001004333.5	ENSP00000468923.2
RNASEK-C17orf49	ENST00000547302.3	c.141+107C>G		intron_variant	Intron 2 of 6	5		ENSP00000450085.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000252 AC: 3 AN: 1192538 Hom.: 0 Cov.: 15 AF XY: 0.00000336 AC XY: 2 AN XY: 595984

African (AFR) AF: 0.00 AC: 0 AN: 27202

American (AMR) AF: 0.00 AC: 0 AN: 34888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21580

East Asian (EAS) AF: 0.00 AC: 0 AN: 36152

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3608

European-Non Finnish (NFE) AF: 0.00000222 AC: 2 AN: 901370

Other (OTH) AF: 0.00 AC: 0 AN: 50760

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.8
DANN	Benign	0.59
PhyloP100		0.16
PromoterAI		0.0038	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;