14-20801679-C-G

Variant names:

• chr14-20801679-C-G
• NM_002933.5:c.390G>C
• RNASE1 p.Lys130Asn

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002933.5(RNASE1):​c.390G>C​(p.Lys130Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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: 32)
• Consequence: RNASE1 NM_002933.5 missense
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1658864).

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.390G>C	p.Lys130Asn	missense	Exon 2 of 2	NP_002924.1	P07998
	RNASE1	NM_198232.3		c.390G>C	p.Lys130Asn	missense	Exon 2 of 2	NP_937875.1	P07998
	RNASE1	NM_198234.3		c.390G>C	p.Lys130Asn	missense	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.390G>C	p.Lys130Asn	missense	Exon 2 of 2	ENSP00000381057.4	P07998
	RNASE1	ENST00000397970.4	TSL:1	c.390G>C	p.Lys130Asn	missense	Exon 3 of 3	ENSP00000381060.4	P07998
	RNASE1	ENST00000340900.3	TSL:2	c.390G>C	p.Lys130Asn	missense	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
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.47
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-5.7
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.26
Sift	Benign	0.30	T
Sift4G	Benign	0.44	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.53
Mutation Taster		=94/6	polymorphism

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

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

Other links and lift over

hg19: chr14-21269838;