17-35258973-T-G

Variant names:

• chr17-35258973-T-G
• NM_144975.4:c.283T>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.283T>G​(p.Phe95Val) 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. 13/21 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: -0.885

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=0.21717387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN5	NM_144975.4	c.283T>G	p.Phe95Val	missense_variant	Exon 2 of 5	ENST00000299977.9	NP_659412.3
SLFN5	NM_001330183.2	c.283T>G	p.Phe95Val	missense_variant	Exon 2 of 4		NP_001317112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN5	ENST00000299977.9	c.283T>G	p.Phe95Val	missense_variant	Exon 2 of 5	1	NM_144975.4	ENSP00000299977.3
SLFN5	ENST00000592325.1	c.283T>G	p.Phe95Val	missense_variant	Exon 2 of 2	1		ENSP00000466984.1
SLFN5	ENST00000542451.1	c.283T>G	p.Phe95Val	missense_variant	Exon 2 of 4	2		ENSP00000440537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.283T>G (p.F95V) 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 283, causing the phenylalanine (F) at amino acid position 95 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	0.30
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.065	T;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.;M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.1	D;D;.
REVEL	Benign	0.087
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.021	D;T;T
Polyphen		0.89	P;D;D
Vest4		0.58
MutPred		0.56		Loss of ubiquitination at K100 (P = 0.0982);Loss of ubiquitination at K100 (P = 0.0982);Loss of ubiquitination at K100 (P = 0.0982);
MVP		0.061
MPC		0.35
ClinPred		0.76	D
GERP RS		2.6
Varity_R		0.62
gMVP		0.16

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: chr17-33585992;