17-35422104-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018042.5(SLFN12):​c.925C>A​(p.Arg309Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SLFN12
NM_018042.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.263
Variant links:
Genes affected
SLFN12 (HGNC:25500): (schlafen family member 12) Predicted to act upstream of or within negative regulation of cell population proliferation. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21097267).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLFN12NM_018042.5 linkc.925C>A p.Arg309Ser missense_variant 2/4 ENST00000304905.10 NP_060512.3 Q8IYM2
SLFN12NM_001289009.2 linkc.925C>A p.Arg309Ser missense_variant 2/4 NP_001275938.1 Q8IYM2
SLFN12XM_005257995.6 linkc.925C>A p.Arg309Ser missense_variant 3/5 XP_005258052.1 Q8IYM2
SLFN12XM_024450822.2 linkc.925C>A p.Arg309Ser missense_variant 4/6 XP_024306590.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLFN12ENST00000304905.10 linkc.925C>A p.Arg309Ser missense_variant 2/41 NM_018042.5 ENSP00000302077.5 Q8IYM2
SLFN12ENST00000394562.5 linkc.925C>A p.Arg309Ser missense_variant 4/61 ENSP00000378063.1 Q8IYM2
SLFN12ENST00000452764.3 linkc.925C>A p.Arg309Ser missense_variant 2/42 ENSP00000394903.2 Q8IYM2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33

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 GeneticsOct 16, 2024The c.925C>A (p.R309S) alteration is located in exon 2 (coding exon 1) of the SLFN12 gene. This alteration results from a C to A substitution at nucleotide position 925, causing the arginine (R) at amino acid position 309 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
Uncertain
0.47
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
7.5
DANN
Uncertain
0.97
DEOGEN2
Benign
0.022
T;T;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.74
.;.;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M;M;M
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-2.4
N;N;N
REVEL
Benign
0.13
Sift
Benign
0.057
T;T;T
Sift4G
Benign
0.10
T;T;T
Polyphen
0.83
P;P;P
Vest4
0.14
MutPred
0.54
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.51
MPC
0.17
ClinPred
0.47
T
GERP RS
-0.76
Varity_R
0.13
gMVP
0.49

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: chr17-33749123; API