chr17-35352796-T-C

Variant names:

• chr17-35352796-T-C
• rs1041163796
• NM_001376007.1:c.2266A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376007.1(SLFN11):​c.2266A>G​(p.Ile756Val) 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 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. I756L) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.108252764).

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.2266A>G	p.Ile756Val	missense	Exon 7 of 7	NP_001362936.1	Q7Z7L1
	SLFN11	NM_001104587.2		c.2266A>G	p.Ile756Val	missense	Exon 7 of 7	NP_001098057.1	Q7Z7L1
	SLFN11	NM_001104588.2		c.2266A>G	p.Ile756Val	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.2266A>G	p.Ile756Val	missense	Exon 7 of 7	ENSP00000510787.1	Q7Z7L1
	SLFN11	ENST00000308377.8	TSL:1	c.2266A>G	p.Ile756Val	missense	Exon 5 of 5	ENSP00000312402.4	Q7Z7L1
	SLFN11	ENST00000394566.5	TSL:2	c.2266A>G	p.Ile756Val	missense	Exon 7 of 7	ENSP00000378067.1	Q7Z7L1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 8.99e-7 AC: 1 AN: 1112010

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.8
DANN	Benign	0.86
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.45
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.050
Sift	Benign	0.33	T
Sift4G	Benign	0.38	T
Polyphen		0.92	P
Vest4		0.14
MutPred		0.32		Gain of helix (P = 0.132)
MVP		0.20
MPC		0.028
ClinPred		0.15	T
GERP RS		0.45
PromoterAI		0.0060	Neutral
Varity_R		0.017
gMVP		0.065

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: rs1041163796; hg19: chr17-33679815; COSMIC: COSV57699831;