rs775747386

Variant names:

• chr17-35352369-C-A
• NM_001376007.1:c.2693G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-35352369-C-A
• chr17-35352369-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376007.1(SLFN11):​c.2693G>T​(p.Trp898Leu) 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 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. W898S) 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: -4.49

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07459983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN11	NM_001376007.1	c.2693G>T	p.Trp898Leu	missense_variant	Exon 7 of 7	ENST00000685675.1	NP_001362936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN11	ENST00000685675.1	c.2693G>T	p.Trp898Leu	missense_variant	Exon 7 of 7		NM_001376007.1	ENSP00000510787.1
SLFN11	ENST00000308377.8	c.2693G>T	p.Trp898Leu	missense_variant	Exon 5 of 5	1		ENSP00000312402.4
SLFN11	ENST00000394566.5	c.2693G>T	p.Trp898Leu	missense_variant	Exon 7 of 7	2		ENSP00000378067.1
SLFN11	ENST00000592108	c.*502G>T		3_prime_UTR_variant	Exon 2 of 2	5		ENSP00000465198.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461392 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726894

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0080
DANN	Benign	0.73
DEOGEN2	Benign	0.0023	T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.35	.;T
M_CAP	Benign	0.00060	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.55	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.42	N;N
REVEL	Benign	0.0040
Sift	Benign	0.081	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.42		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.095
MPC		0.035
ClinPred		0.056	T
GERP RS		-5.0
Varity_R		0.040
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33679388;