dbSNP rs761087261: SLFN11:p.Arg798Leu (chr17-35352669-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001376007.1(SLFN11):c.2393G>T(p.Arg798Leu) 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 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. R798C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLFN11
NM_001376007.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -12.0

Publications

0 publications found

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]

SLFN11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044324845).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376007.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLFN11	NM_001376007.1	MANE Select	c.2393G>T	p.Arg798Leu	missense	Exon 7 of 7	NP_001362936.1	Q7Z7L1
SLFN11	NM_001104587.2		c.2393G>T	p.Arg798Leu	missense	Exon 7 of 7	NP_001098057.1	Q7Z7L1
SLFN11	NM_001104588.2		c.2393G>T	p.Arg798Leu	missense	Exon 7 of 7	NP_001098058.1	Q7Z7L1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLFN11	ENST00000685675.1	MANE Select	c.2393G>T	p.Arg798Leu	missense	Exon 7 of 7	ENSP00000510787.1	Q7Z7L1
SLFN11	ENST00000308377.8	TSL:1	c.2393G>T	p.Arg798Leu	missense	Exon 5 of 5	ENSP00000312402.4	Q7Z7L1
SLFN11	ENST00000394566.5	TSL:2	c.2393G>T	p.Arg798Leu	missense	Exon 7 of 7	ENSP00000378067.1	Q7Z7L1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111936

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.0010

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.0064

Eigen

Benign

-2.9

Eigen_PC

Benign

-3.0

FATHMM_MKL

Benign

0.00068

LIST_S2

Benign

0.058

M_CAP

Benign

0.015

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.73

MutationAssessor

Benign

-0.49

PhyloP100

-12

PrimateAI

Benign

0.24

PROVEAN

Benign

0.39

REVEL

Benign

0.26

Sift

Benign

0.65

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.18

MutPred

0.42

Loss of phosphorylation at T795 (P = 0.0758)

MVP

0.24

MPC

0.029

ClinPred

0.028

GERP RS

-8.0

PromoterAI

0.017

Neutral

(source)

Varity_R

0.058

gMVP

0.19

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over