rs776647622

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001376007.1(SLFN11):​c.2564G>C​(p.Arg855Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R855Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SLFN11
NM_001376007.1 missense

Scores

5
6
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.522
Variant links:
Genes affected
SLFN11 (HGNC:26633): (schlafen family member 11) Enables tRNA binding activity. Involved in several processes, including defense response to virus; negative regulation of G1/S transition of mitotic cell cycle; and replication fork arrest. Located in cytosol; nucleoplasm; and site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
SLFN11NM_001376007.1 linkc.2564G>C p.Arg855Pro missense_variant Exon 7 of 7 ENST00000685675.1 NP_001362936.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLFN11ENST00000685675.1 linkc.2564G>C p.Arg855Pro missense_variant Exon 7 of 7 NM_001376007.1 ENSP00000510787.1 Q7Z7L1
SLFN11ENST00000308377.8 linkc.2564G>C p.Arg855Pro missense_variant Exon 5 of 5 1 ENSP00000312402.4 Q7Z7L1
SLFN11ENST00000394566.5 linkc.2564G>C p.Arg855Pro missense_variant Exon 7 of 7 2 ENSP00000378067.1 Q7Z7L1
SLFN11ENST00000592108 linkc.*373G>C 3_prime_UTR_variant Exon 2 of 2 5 ENSP00000465198.1 K7EJJ3

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;T
Eigen
Benign
-0.016
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.69
.;T
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.61
D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Pathogenic
2.9
M;M
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-4.6
D;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.027
D;D
Sift4G
Uncertain
0.012
D;D
Polyphen
1.0
D;D
Vest4
0.58
MutPred
0.52
Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP
0.55
MPC
0.24
ClinPred
0.98
D
GERP RS
2.0
Varity_R
0.68
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: chr17-33679517; API