Menu
GeneBe

14-20801971-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002933.5(RNASE1):c.98C>T(p.Ala33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.25
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNASE1NM_002933.5 linkuse as main transcriptc.98C>T p.Ala33Val missense_variant 2/2 ENST00000397967.5
LOC105370397XR_007064063.1 linkuse as main transcriptn.277-7868G>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.98C>T p.Ala33Val 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 GeneticsJun 22, 2023The c.98C>T (p.A33V) alteration is located in exon 3 (coding exon 1) of the RNASE1 gene. This alteration results from a C to T substitution at nucleotide position 98, causing the alanine (A) at amino acid position 33 to be replaced by a valine (V). 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
0.32
BayesDel_addAF
Benign
0.0068
T
BayesDel_noAF
Benign
-0.23
Cadd
Benign
15
Dann
Uncertain
1.0
DEOGEN2
Benign
0.39
T;T;T;T
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.055
FATHMM_MKL
Benign
0.14
N
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.58
D;D;D;D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Pathogenic
3.1
M;M;M;M
MutationTaster
Benign
1.0
D;N;N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Uncertain
0.45
Sift
Benign
0.046
D;D;D;D
Sift4G
Benign
0.20
T;T;T;T
Polyphen
1.0
D;D;D;D
Vest4
0.28
MutPred
0.69
Gain of methylation at K34 (P = 0.0497);Gain of methylation at K34 (P = 0.0497);Gain of methylation at K34 (P = 0.0497);Gain of methylation at K34 (P = 0.0497);
MVP
0.85
MPC
0.23
ClinPred
0.94
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.29
gMVP
0.72

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: chr14-21270130; API