NM_144975.4:c.137C>G

Variant names:

• chr17-35258827-C-G
• rs748656300
• NM_144975.4:c.137C>G

Variant summary

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

The NM_144975.4(SLFN5):​c.137C>G​(p.Ala46Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A46V) 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: 1.57
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.137C>G	p.Ala46Gly	missense	Exon 2 of 5	NP_659412.3
	SLFN5	NM_001330183.2		c.137C>G	p.Ala46Gly	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.137C>G	p.Ala46Gly	missense	Exon 2 of 5	ENSP00000299977.3	Q08AF3-1
	SLFN5	ENST00000592325.1	TSL:1	c.137C>G	p.Ala46Gly	missense	Exon 2 of 2	ENSP00000466984.1	Q08AF3-2
	SLFN5	ENST00000884250.1		c.137C>G	p.Ala46Gly	missense	Exon 2 of 5	ENSP00000554309.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.075
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0099	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.62		Loss of stability (P = 0.0489)
MVP		0.19
MPC		0.28
ClinPred		0.93	D
GERP RS		3.7
Varity_R		0.60
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs748656300; hg19: chr17-33585846;