rs142470821

Variant names:

• chr17-35352709-C-A
• rs142470821
• NM_001376007.1:c.2353G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-35352709-C-A
• chr17-35352709-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001376007.1(SLFN11):​c.2353G>T​(p.Val785Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 1,614,208 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: SLFN11 NM_001376007.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.93
• Publications: 5 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00920403).
• BP6: Variant 17-35352709-C-A is Benign according to our data. Variant chr17-35352709-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2217311.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2353G>T	p.Val785Leu	missense	Exon 7 of 7	NP_001362936.1	Q7Z7L1
	SLFN11	NM_001104587.2		c.2353G>T	p.Val785Leu	missense	Exon 7 of 7	NP_001098057.1	Q7Z7L1
	SLFN11	NM_001104588.2		c.2353G>T	p.Val785Leu	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.2353G>T	p.Val785Leu	missense	Exon 7 of 7	ENSP00000510787.1	Q7Z7L1
	SLFN11	ENST00000308377.8	TSL:1	c.2353G>T	p.Val785Leu	missense	Exon 5 of 5	ENSP00000312402.4	Q7Z7L1
	SLFN11	ENST00000394566.5	TSL:2	c.2353G>T	p.Val785Leu	missense	Exon 7 of 7	ENSP00000378067.1	Q7Z7L1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152208 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000398 AC: 100 AN: 251402 AF XY: 0.000390

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000457

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000258 AC: 377 AN: 1461882 Hom.: 1 Cov.: 33 AF XY: 0.000271 AC XY: 197 AN XY: 727238

African (AFR) AF: 0.00114 AC: 38 AN: 33480

American (AMR) AF: 0.000783 AC: 35 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.000216 AC: 240 AN: 1112002

Other (OTH) AF: 0.000613 AC: 37 AN: 60396

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152326 Hom.: 0 Cov.: 30 AF XY: 0.000362 AC XY: 27 AN XY: 74484

African (AFR) AF: 0.000866 AC: 36 AN: 41578

American (AMR) AF: 0.000392 AC: 6 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68034

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000471 Hom.: 1

Bravo AF: 0.000623

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000395 AC: 48

EpiCase AF: 0.000818

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.12
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.0010
DANN	Benign	0.13
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.00092	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0092	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	-0.95	N
PhyloP100		-6.9
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.98	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.025
MutPred		0.37		Loss of catalytic residue at V785 (P = 0.0522)
MVP		0.18
MPC		0.026
ClinPred		0.021	T
GERP RS		-8.0
PromoterAI		0.0090	Neutral
Varity_R		0.013
gMVP		0.13
Mutation Taster		=100/0	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: rs142470821; hg19: chr17-33679728;