Menu
GeneBe

14-20801920-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002933.5(RNASE1):c.149G>T(p.Ser50Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RNASE1
NM_002933.5 missense

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.39
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.20527756).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNASE1NM_002933.5 linkuse as main transcriptc.149G>T p.Ser50Ile missense_variant 2/2 ENST00000397967.5
LOC105370397XR_007064063.1 linkuse as main transcriptn.277-7919C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNASE1ENST00000397967.5 linkuse as main transcriptc.149G>T p.Ser50Ile missense_variant 2/21 NM_002933.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 24, 2023The c.149G>T (p.S50I) alteration is located in exon 3 (coding exon 1) of the RNASE1 gene. This alteration results from a G to T substitution at nucleotide position 149, causing the serine (S) at amino acid position 50 to be replaced by an isoleucine (I). 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
0.29
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
Cadd
Benign
7.8
Dann
Uncertain
0.98
DEOGEN2
Benign
0.38
T;T;T;T;T
Eigen
Benign
-0.88
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.035
N
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.21
T;T;T;T;T
MetaSVM
Uncertain
-0.030
T
MutationAssessor
Pathogenic
3.1
M;M;M;.;M
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.6
D;D;D;D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D
Polyphen
0.93
P;P;P;.;P
Vest4
0.18
MutPred
0.45
Gain of catalytic residue at S48 (P = 0.0065);Gain of catalytic residue at S48 (P = 0.0065);Gain of catalytic residue at S48 (P = 0.0065);.;Gain of catalytic residue at S48 (P = 0.0065);
MVP
0.69
MPC
0.56
ClinPred
0.93
D
GERP RS
-9.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.42
gMVP
0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-21270079; API