chr17-35352459-A-G

Position:

• chr17-35352459-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001376007.1(SLFN11):​c.2603T>C​(p.Ile868Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLFN11 NM_001376007.1 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.71

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.847
• PP5: Variant 17-35352459-A-G is Pathogenic according to our data. Variant chr17-35352459-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 982226.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLFN11	NM_001376007.1	c.2603T>C	p.Ile868Thr	missense_variant	7/7	ENST00000685675.1	NP_001362936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLFN11	ENST00000685675.1	c.2603T>C	p.Ile868Thr	missense_variant	7/7		NM_001376007.1	ENSP00000510787.1
SLFN11	ENST00000308377.8	c.2603T>C	p.Ile868Thr	missense_variant	5/5	1		ENSP00000312402.4
SLFN11	ENST00000394566.5	c.2603T>C	p.Ile868Thr	missense_variant	7/7	2		ENSP00000378067.1
SLFN11	ENST00000592108.1	c.*412T>C		3_prime_UTR_variant	2/2	5		ENSP00000465198.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Moyamoya angiopathy Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.075
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.61
MutPred		0.73		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.23
MPC		0.22
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.23
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs1203408796; hg19: chr17-33679478;