17-35259168-G-A

Variant names:

• chr17-35259168-G-A
• rs199778009
• NM_144975.4:c.478G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144975.4(SLFN5):​c.478G>A​(p.Gly160Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G160R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN5 NM_144975.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052518874).

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.478G>A	p.Gly160Ser	missense	Exon 2 of 5	NP_659412.3
	SLFN5	NM_001330183.2		c.478G>A	p.Gly160Ser	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.478G>A	p.Gly160Ser	missense	Exon 2 of 5	ENSP00000299977.3	Q08AF3-1
	SLFN5	ENST00000592325.1	TSL:1	c.478G>A	p.Gly160Ser	missense	Exon 2 of 2	ENSP00000466984.1	Q08AF3-2
	SLFN5	ENST00000884250.1		c.478G>A	p.Gly160Ser	missense	Exon 2 of 5	ENSP00000554309.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.35
DANN	Benign	0.51
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.10
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.0090
Sift	Benign	0.75	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.25		Loss of sheet (P = 0.0457)
MVP		0.030
MPC		0.065
ClinPred		0.019	T
GERP RS		1.4
Varity_R		0.014
gMVP		0.079

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

dbSNP: rs199778009; hg19: chr17-33586187;