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GeneBe

14-20782112-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005615.5(RNASE6):c.413C>G(p.Pro138Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 152090 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

RNASE6
NM_005615.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.600

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.052167445).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNASE6NM_005615.5 linkuse as main transcriptc.413C>G p.Pro138Arg missense_variant 2/2 ENST00000304677.3
LOC107984671XR_001750624.2 linkuse as main transcriptn.626+17792G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNASE6ENST00000304677.3 linkuse as main transcriptc.413C>G p.Pro138Arg missense_variant 2/21 NM_005615.5 P1

Frequencies

GnomAD3 genomes
AF:
0.000283
AC:
43
AN:
152090
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000894
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000771
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000116
AC:
29
AN:
248942
Hom.:
0
AF XY:
0.000134
AC XY:
18
AN XY:
134472
show subpopulations
Gnomad AFR exome
AF:
0.000677
Gnomad AMR exome
AF:
0.0000582
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000653
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000644
AC:
94
AN:
1459876
Hom.:
0
AF XY:
0.0000592
AC XY:
43
AN XY:
726128
show subpopulations
Gnomad4 AFR exome
AF:
0.000866
Gnomad4 AMR exome
AF:
0.0000673
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000479
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000342
Gnomad4 OTH exome
AF:
0.0000166
Alfa
AF:
0.0000904
Hom.:
0
Bravo
AF:
0.000287
ExAC
AF:
0.000148
AC:
18

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 12, 2022The c.413C>G (p.P138R) alteration is located in exon 2 (coding exon 1) of the RNASE6 gene. This alteration results from a C to G substitution at nucleotide position 413, causing the proline (P) at amino acid position 138 to be replaced by an arginine (R). 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
0.11
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.68
Cadd
Benign
17
Dann
Uncertain
0.99
DEOGEN2
Benign
0.026
T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.072
T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.052
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
M
MutationTaster
Benign
0.98
N
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.018
Sift
Benign
0.10
T
Sift4G
Benign
0.12
T
Polyphen
1.0
D
Vest4
0.20
MVP
0.41
MPC
0.20
ClinPred
0.038
T
GERP RS
0.73
Varity_R
0.26
gMVP
0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199597118; hg19: chr14-21250271; API