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GeneBe

14-20781868-A-T

Variant summary

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

The NM_005615.5(RNASE6):c.169A>T(p.Thr57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. 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: not found (cov: 32)

Consequence

RNASE6
NM_005615.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

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, Median coverage is 32.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.120704174).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNASE6NM_005615.5 linkuse as main transcriptc.169A>T p.Thr57Ser missense_variant 2/2 ENST00000304677.3
LOC107984671XR_001750624.2 linkuse as main transcriptn.626+18036T>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNASE6ENST00000304677.3 linkuse as main transcriptc.169A>T p.Thr57Ser missense_variant 2/21 NM_005615.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32

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 GeneticsAug 02, 2023The c.169A>T (p.T57S) alteration is located in exon 2 (coding exon 1) of the RNASE6 gene. This alteration results from a A to T substitution at nucleotide position 169, causing the threonine (T) at amino acid position 57 to be replaced by a serine (S). 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
0.16
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
Cadd
Benign
11
Dann
Benign
0.97
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.075
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.042
Sift
Benign
0.082
T
Sift4G
Benign
0.27
T
Polyphen
0.53
P
Vest4
0.16
MutPred
0.28
Gain of disorder (P = 0.0323);
MVP
0.49
MPC
0.18
ClinPred
0.26
T
GERP RS
3.9
Varity_R
0.37
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr14-21250027; API