RNASE1 p.Lys130Lys

Variant names:

• chr14-20801678-C-C
• NM_002933.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr14-20801679--
• chr14-20801679-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002933.5(RNASE1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASE1 NM_002933.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.73
• Publications: 0 publications found

Genes affected

RNASE1 (HGNC:10044): (ribonuclease A family member 1, pancreatic) This gene encodes a member of the pancreatic-type of secretory ribonucleases, a subset of the ribonuclease A superfamily. The encoded endonuclease cleaves internal phosphodiester RNA bonds on the 3'-side of pyrimidine bases. It prefers poly(C) as a substrate and hydrolyzes 2',3'-cyclic nucleotides, with a pH optimum near 8.0. The encoded protein is monomeric and more commonly acts to degrade ds-RNA over ss-RNA. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

ENSG00000303743 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002933.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE1	NM_002933.5	MANE Select	c.		exon_region	Exon 2 of 2	NP_002924.1	P07998
	RNASE1	NM_198232.3		c.		exon_region	Exon 2 of 2	NP_937875.1	P07998
	RNASE1	NM_198234.3		c.		exon_region	Exon 3 of 3	NP_937877.1	P07998

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE1	ENST00000397967.5	TSL:1 MANE Select	c.		exon_region	Exon 2 of 2	ENSP00000381057.4	P07998
	RNASE1	ENST00000397970.4	TSL:1	c.		exon_region	Exon 3 of 3	ENSP00000381060.4	P07998
	RNASE1	ENST00000340900.3	TSL:2	c.		exon_region	Exon 3 of 3	ENSP00000344193.3	P07998

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-21269837;