dbSNP rs73278963: SLFN5:p.Lys59Arg (chr17-35258866-A-G) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_144975.4(SLFN5):c.176A>G(p.Lys59Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,614,198 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 38 hom. )

Consequence

SLFN5
NM_144975.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.230

Variant links:

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]

SLFN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity SLFN5_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0023961067).

BP6

Variant 17-35258866-A-G is Benign according to our data. Variant chr17-35258866-A-G is described in ClinVar as [Benign]. Clinvar id is 781278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1670/152304) while in subpopulation AFR AF= 0.0378 (1571/41556). AF 95% confidence interval is 0.0362. There are 23 homozygotes in gnomad4. There are 798 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN5	NM_144975.4 link	c.176A>G	p.Lys59Arg	missense_variant	Exon 2 of 5	ENST00000299977.9	NP_659412.3	Q08AF3-1
SLFN5	NM_001330183.2 link	c.176A>G	p.Lys59Arg	missense_variant	Exon 2 of 4		NP_001317112.1	B4E128

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLFN5	ENST00000299977.9 link	c.176A>G	p.Lys59Arg	missense_variant	Exon 2 of 5	1	NM_144975.4	ENSP00000299977.3	Q08AF3-1
SLFN5	ENST00000592325.1 link	c.176A>G	p.Lys59Arg	missense_variant	Exon 2 of 2	1		ENSP00000466984.1	Q08AF3-2
SLFN5	ENST00000542451.1 link	c.176A>G	p.Lys59Arg	missense_variant	Exon 2 of 4	2		ENSP00000440537.1	B4E128

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1667

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00305

AC:

767

AN:

251462

Hom.:

AF XY:

0.00215

AC XY:

292

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0402

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00125

AC:

1830

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

803

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0422

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00346

GnomAD4 genome

AF:

0.0110

AC:

1670

AN:

152304

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

798

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0378

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.0126

ESP6500AA

AF:

0.0397

AC:

175

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00377

AC:

458

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;.;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.41

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.45

N;N;.

REVEL

Benign

0.031

Sift

Benign

0.47

T;T;.

Sift4G

Benign

0.38

T;T;T

Polyphen

0.054

B;B;P

Vest4

0.20

MVP

0.085

MPC

0.059

ClinPred

0.0022

GERP RS

1.2

Varity_R

0.041

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over