17-35352670-G-A

Variant names:

• chr17-35352670-G-A
• rs766672845
• NM_001376007.1:c.2392C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001376007.1(SLFN11):​c.2392C>T​(p.Arg798Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R798H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SLFN11 NM_001376007.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.46
• Publications: 0 publications found

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]

ACMG classification

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=0.05526477).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN11	NM_001376007.1	MANE Select	c.2392C>T	p.Arg798Cys	missense	Exon 7 of 7	NP_001362936.1	Q7Z7L1
	SLFN11	NM_001104587.2		c.2392C>T	p.Arg798Cys	missense	Exon 7 of 7	NP_001098057.1	Q7Z7L1
	SLFN11	NM_001104588.2		c.2392C>T	p.Arg798Cys	missense	Exon 7 of 7	NP_001098058.1	Q7Z7L1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN11	ENST00000685675.1	MANE Select	c.2392C>T	p.Arg798Cys	missense	Exon 7 of 7	ENSP00000510787.1	Q7Z7L1
	SLFN11	ENST00000308377.8	TSL:1	c.2392C>T	p.Arg798Cys	missense	Exon 5 of 5	ENSP00000312402.4	Q7Z7L1
	SLFN11	ENST00000394566.5	TSL:2	c.2392C>T	p.Arg798Cys	missense	Exon 7 of 7	ENSP00000378067.1	Q7Z7L1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152118 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251384 AF XY: 0.0000147

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461668 Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11 AN XY: 727136

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111936

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152118 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.0000241 AC: 1 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.0090
DANN	Benign	0.47
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.6
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.088	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	-0.35	N
PhyloP100		-6.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.050	N
REVEL	Uncertain	0.31
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.43		Loss of catalytic residue at R798 (P = 0.0664)
MVP		0.28
MPC		0.031
ClinPred		0.056	T
GERP RS		-8.0
PromoterAI		0.038	Neutral
Varity_R		0.055
gMVP		0.15
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs766672845; hg19: chr17-33679689; COSMIC: COSV57698711;