17-35258721-T-C

Variant names:

• chr17-35258721-T-C
• NM_144975.4:c.31T>C

Variant summary

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

The NM_144975.4(SLFN5):​c.31T>C​(p.Phe11Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 4.09
• Publications: 0 publications found

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

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=0.18523484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144975.4. 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
	SLFN5	NM_144975.4	MANE Select	c.31T>C	p.Phe11Leu	missense	Exon 2 of 5	NP_659412.3
	SLFN5	NM_001330183.2		c.31T>C	p.Phe11Leu	missense	Exon 2 of 4	NP_001317112.1	B4E128

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN5	ENST00000299977.9	TSL:1 MANE Select	c.31T>C	p.Phe11Leu	missense	Exon 2 of 5	ENSP00000299977.3	Q08AF3-1
	SLFN5	ENST00000592325.1	TSL:1	c.31T>C	p.Phe11Leu	missense	Exon 2 of 2	ENSP00000466984.1	Q08AF3-2
	SLFN5	ENST00000884250.1		c.31T>C	p.Phe11Leu	missense	Exon 2 of 5	ENSP00000554309.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.85
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.1
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.015	D
Polyphen		0.44	B
Vest4		0.49
MutPred		0.56		Gain of sheet (P = 0.1208)
MVP		0.14
MPC		0.12
ClinPred		0.69	D
GERP RS		3.8
Varity_R		0.39
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

Other links and lift over

hg19: chr17-33585740;