chr17-35352408-A-G

Variant names:

• chr17-35352408-A-G
• NM_001376007.1:c.2654T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001376007.1(SLFN11):​c.2654T>C​(p.Leu885Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLFN11 NM_001376007.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

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.2654T>C	p.Leu885Pro	missense	Exon 7 of 7	NP_001362936.1	Q7Z7L1
	SLFN11	NM_001104587.2		c.2654T>C	p.Leu885Pro	missense	Exon 7 of 7	NP_001098057.1	Q7Z7L1
	SLFN11	NM_001104588.2		c.2654T>C	p.Leu885Pro	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.2654T>C	p.Leu885Pro	missense	Exon 7 of 7	ENSP00000510787.1	Q7Z7L1
	SLFN11	ENST00000308377.8	TSL:1	c.2654T>C	p.Leu885Pro	missense	Exon 5 of 5	ENSP00000312402.4	Q7Z7L1
	SLFN11	ENST00000394566.5	TSL:2	c.2654T>C	p.Leu885Pro	missense	Exon 7 of 7	ENSP00000378067.1	Q7Z7L1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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	0.84
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.8
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.69		Loss of helix (P = 0.0093)
MVP		0.60
MPC		0.25
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.85
gMVP		0.52

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

hg19: chr17-33679427;