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GeneBe

14-20782062-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate

The NM_005615.5(RNASE6):c.363G>C(p.Gln121His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152144 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

RNASE6
NM_005615.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.55

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.00000657 (1/152144) while in subpopulation AFR AF= 0.0000241 (1/41424). AF 95% confidence interval is 0. There are 0 homozygotes in gnomad. There are 1 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19365028).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNASE6NM_005615.5 linkuse as main transcriptc.363G>C p.Gln121His missense_variant 2/2 ENST00000304677.3
LOC107984671XR_001750624.2 linkuse as main transcriptn.626+17842C>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNASE6ENST00000304677.3 linkuse as main transcriptc.363G>C p.Gln121His missense_variant 2/21 NM_005615.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251438
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461892
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00

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 GeneticsNov 10, 2022The c.363G>C (p.Q121H) alteration is located in exon 2 (coding exon 1) of the RNASE6 gene. This alteration results from a G to C substitution at nucleotide position 363, causing the glutamine (Q) at amino acid position 121 to be replaced by a histidine (H). 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
0.21
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.49
Cadd
Benign
0.28
Dann
Benign
0.94
DEOGEN2
Benign
0.089
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.19
T
MetaSVM
Uncertain
-0.075
T
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.29
Sift
Benign
0.12
T
Sift4G
Benign
0.12
T
Polyphen
0.91
P
Vest4
0.073
MutPred
0.30
Loss of catalytic residue at Q121 (P = 0.0521);
MVP
0.59
MPC
0.097
ClinPred
0.64
D
GERP RS
-10
Varity_R
0.32
gMVP
0.29

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: rs372433350; hg19: chr14-21250221; API