17-35440609-A-G

Variant names:

• chr17-35440609-A-G
• NM_144682.6:c.2680T>C

Variant summary

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

The NM_144682.6(SLFN13):​c.2680T>C​(p.Tyr894His) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN13 NM_144682.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• Publications: 0 publications found

Genes affected

SLFN13 (HGNC:26481): (schlafen family member 13) Enables endoribonuclease activity. Involved in rRNA catabolic process and tRNA catabolic process. Located in cytoplasm. [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=0.109684914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN13	NM_144682.6	c.2680T>C	p.Tyr894His	missense_variant	Exon 6 of 6	ENST00000285013.11	NP_653283.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN13	ENST00000285013.11	c.2680T>C	p.Tyr894His	missense_variant	Exon 6 of 6	1	NM_144682.6	ENSP00000285013.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2680T>C (p.Y894H) alteration is located in exon 6 (coding exon 4) of the SLFN13 gene. This alteration results from a T to C substitution at nucleotide position 2680, causing the tyrosine (Y) at amino acid position 894 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.016	T;T;T;.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.68	.;.;T;T;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.6	L;L;L;.;L
PhyloP100		2.4
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.4	D;D;D;D;.
REVEL	Benign	0.15
Sift	Benign	0.10	T;T;T;T;.
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.0050	B;B;B;B;B
Vest4		0.12
MutPred		0.56		Gain of disorder (P = 0.0032);Gain of disorder (P = 0.0032);Gain of disorder (P = 0.0032);.;Gain of disorder (P = 0.0032);
MVP		0.28
MPC		0.054
ClinPred		0.49	T
GERP RS		2.2
Varity_R		0.18
gMVP		0.21

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: chr17-33767628;