chr17-35352422-A-T

Variant names:

• chr17-35352422-A-T
• rs141788369
• NM_001376007.1:c.2640T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001376007.1(SLFN11):​c.2640T>A​(p.Asn880Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,132 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SLFN11 NM_001376007.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.129
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13463894).

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.2640T>A	p.Asn880Lys	missense	Exon 7 of 7	NP_001362936.1	Q7Z7L1
	SLFN11	NM_001104587.2		c.2640T>A	p.Asn880Lys	missense	Exon 7 of 7	NP_001098057.1	Q7Z7L1
	SLFN11	NM_001104588.2		c.2640T>A	p.Asn880Lys	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.2640T>A	p.Asn880Lys	missense	Exon 7 of 7	ENSP00000510787.1	Q7Z7L1
	SLFN11	ENST00000308377.8	TSL:1	c.2640T>A	p.Asn880Lys	missense	Exon 5 of 5	ENSP00000312402.4	Q7Z7L1
	SLFN11	ENST00000394566.5	TSL:2	c.2640T>A	p.Asn880Lys	missense	Exon 7 of 7	ENSP00000378067.1	Q7Z7L1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152242 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000437 AC: 11 AN: 251486 AF XY: 0.0000294

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.0000867

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: 0.0000137 AC: 20 AN: 1461890 Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11 AN XY: 727246

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152242 Hom.: 0 Cov.: 30 AF XY: 0.000161 AC XY: 12 AN XY: 74388

African (AFR) AF: 0.000506 AC: 21 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

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

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000132

ExAC AF: 0.0000247 AC: 3

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	Pathogenic	0.66
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.13
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.26
Sift	Benign	0.37	T
Sift4G	Benign	0.15	T
Polyphen		0.99	D
Vest4		0.34
MutPred		0.64		Gain of methylation at N880 (P = 0.0024)
MVP		0.29
MPC		0.19
ClinPred		0.11	T
GERP RS		-2.0
Varity_R		0.052
gMVP		0.27
Mutation Taster		=99/1	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: rs141788369; hg19: chr17-33679441;