GeneBe

17-35440726-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144682.6(SLFN13):​c.2563C>T​(p.Arg855Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

SLFN13
NM_144682.6 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

Publications

7 publications found
Variant links:
Genes affected
SLFN13 (HGNC:26481): (schlafen family member 13) Enables endoribonuclease activity. Involved in rRNA catabolic process and tRNA catabolic process. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLFN13NM_144682.6 linkc.2563C>T p.Arg855Trp missense_variant Exon 6 of 6 ENST00000285013.11 NP_653283.3 Q68D06-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLFN13ENST00000285013.11 linkc.2563C>T p.Arg855Trp missense_variant Exon 6 of 6 1 NM_144682.6 ENSP00000285013.6 Q68D06-1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152052
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000596
AC:
15
AN:
251476
AF XY:
0.0000589
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000791
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000746
AC:
109
AN:
1461856
Hom.:
0
Cov.:
30
AF XY:
0.0000825
AC XY:
60
AN XY:
727224
show subpopulations
African (AFR)
AF:
0.0000896
AC:
3
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39700
South Asian (SAS)
AF:
0.0000696
AC:
6
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000827
AC:
92
AN:
1111998
Other (OTH)
AF:
0.0000994
AC:
6
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
8
16
25
33
41
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152052
Hom.:
0
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74250
show subpopulations
African (AFR)
AF:
0.0000483
AC:
2
AN:
41424
American (AMR)
AF:
0.00
AC:
0
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.000386
AC:
2
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10556
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 16, 2021
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.2563C>T (p.R855W) alteration is located in exon 6 (coding exon 4) of the SLFN13 gene. This alteration results from a C to T substitution at nucleotide position 2563, causing the arginine (R) at amino acid position 855 to be replaced by a tryptophan (W). 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
0.17
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.086
T;T;T;.;T
Eigen
Uncertain
0.30
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.48
.;.;T;T;.
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.54
D;D;D;D;D
MetaSVM
Uncertain
0.33
D
MutationAssessor
Uncertain
2.5
M;M;M;.;M
PhyloP100
2.4
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-5.1
D;D;D;D;.
REVEL
Uncertain
0.54
Sift
Benign
0.031
D;D;D;D;.
Sift4G
Uncertain
0.0020
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.37
MVP
0.84
MPC
0.074
ClinPred
0.99
D
GERP RS
3.3
Varity_R
0.15
gMVP
0.25
Mutation Taster
=85/15
polymorphism

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

Other links and lift over

dbSNP: rs371744448; hg19: chr17-33767745; COSMIC: COSV53192599; COSMIC: COSV53192599; API