Genetic Variant NM_144682.6:c.2455G>C (chr17-35440834-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144682.6(SLFN13):c.2455G>C(p.Val819Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SLFN13
NM_144682.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.413

Publications

0 publications found

Variant links:

Genes affected

SLFN13 (HGNC:26481): (schlafen family member 13) Enables endoribonuclease activity. Involved in rRNA catabolic process and tRNA catabolic process. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SLFN13 links:

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ACMG classification

Classification was made for transcript

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=0.1636666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN13	NM_144682.6 link	c.2455G>C	p.Val819Leu	missense_variant	Exon 6 of 6	ENST00000285013.11	NP_653283.3	Q68D06-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN13	ENST00000285013.11 link	c.2455G>C	p.Val819Leu	missense_variant	Exon 6 of 6	1	NM_144682.6	ENSP00000285013.6		Q68D06-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2455G>C (p.V819L) alteration is located in exon 6 (coding exon 4) of the SLFN13 gene. This alteration results from a G to C substitution at nucleotide position 2455, causing the valine (V) at amino acid position 819 to be replaced by a leucine (L). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0023

T;T;T;.;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.36

.;.;T;T;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.6

M;M;M;.;M

PhyloP100

-0.41

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.3

N;N;N;N;.

REVEL

Benign

0.24

Sift

Benign

0.17

T;T;T;T;.

Sift4G

Benign

0.38

T;T;T;T;T

Polyphen

0.98

D;D;D;P;D

Vest4

0.10

MutPred

0.25

Loss of catalytic residue at V819 (P = 0.0574);Loss of catalytic residue at V819 (P = 0.0574);Loss of catalytic residue at V819 (P = 0.0574);.;Loss of catalytic residue at V819 (P = 0.0574);

MVP

0.73

MPC

0.048

ClinPred

0.37

GERP RS

-2.2

Varity_R

0.057

gMVP

0.15

Mutation Taster

=100/0

polymorphism

(source)

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

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NM_144682.6:c.2455G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over