17-35259213-T-G

Variant summary

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

The NM_144975.4(SLFN5):c.523T>G(p.Leu175Val) 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. 15/21 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: SLFN5 NM_144975.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.395

Genes affected

SLFN5 (HGNC:28286): (schlafen family member 5) Predicted to enable ATP binding activity. Predicted to be involved in cell differentiation. Predicted to be located in nucleus. [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=0.07203311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN5	NM_144975.4	c.523T>G	p.Leu175Val	missense_variant	2/5	ENST00000299977.9
SLFN5	NM_001330183.2	c.523T>G	p.Leu175Val	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN5	ENST00000299977.9	c.523T>G	p.Leu175Val	missense_variant	2/5	1	NM_144975.4	P1
SLFN5	ENST00000592325.1	c.523T>G	p.Leu175Val	missense_variant	2/2	1
SLFN5	ENST00000542451.1	c.523T>G	p.Leu175Val	missense_variant	2/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.523T>G (p.L175V) alteration is located in exon 2 (coding exon 1) of the SLFN5 gene. This alteration results from a T to G substitution at nucleotide position 523, causing the leucine (L) at amino acid position 175 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.70
Dann	Benign	0.94
DEOGEN2	Benign	0.0055	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L;.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.60	N;N;.
REVEL	Benign	0.022
Sift	Benign	0.43	T;T;.
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.21
MutPred		0.48		Gain of methylation at K179 (P = 0.1156);Gain of methylation at K179 (P = 0.1156);Gain of methylation at K179 (P = 0.1156);
MVP		0.099
MPC		0.070
ClinPred		0.073	T
GERP RS		-2.4
Varity_R		0.073
gMVP		0.078

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: rs1459294341; hg19: chr17-33586232;