NM_144975.4:c.597G>T

Variant names:

• chr17-35259287-G-T
• NM_144975.4:c.597G>T

Variant summary

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

The NM_144975.4(SLFN5):​c.597G>T​(p.Met199Ile) 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. 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: -0.216

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=0.18818721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN5	NM_144975.4	c.597G>T	p.Met199Ile	missense_variant	Exon 2 of 5	ENST00000299977.9	NP_659412.3
SLFN5	NM_001330183.2	c.597G>T	p.Met199Ile	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.597G>T	p.Met199Ile	missense_variant	Exon 2 of 5	1	NM_144975.4	ENSP00000299977.3
SLFN5	ENST00000592325.1	c.597G>T	p.Met199Ile	missense_variant	Exon 2 of 2	1		ENSP00000466984.1
SLFN5	ENST00000542451.1	c.597G>T	p.Met199Ile	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

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.597G>T (p.M199I) alteration is located in exon 2 (coding exon 1) of the SLFN5 gene. This alteration results from a G to T substitution at nucleotide position 597, causing the methionine (M) at amino acid position 199 to be replaced by an isoleucine (I). 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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0064	T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.8	D;N;.
REVEL	Benign	0.12
Sift	Uncertain	0.026	D;T;.
Sift4G	Benign	0.12	T;T;T
Polyphen		0.99	D;D;P
Vest4		0.38
MutPred		0.34		Loss of catalytic residue at V195 (P = 0.1052);Loss of catalytic residue at V195 (P = 0.1052);Loss of catalytic residue at V195 (P = 0.1052);
MVP		0.13
MPC		0.38
ClinPred		0.81	D
GERP RS		2.6
Varity_R		0.23
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33586306;