17-35259667-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_144975.4(SLFN5):c.977G>A(p.Arg326Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,600,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SLFN5
NM_144975.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.754

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018826723).

BP6

Variant 17-35259667-G-A is Benign according to our data. Variant chr17-35259667-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2324707.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN5	NM_144975.4 linkuse as main transcript	c.977G>A	p.Arg326Lys	missense_variant	2/5	ENST00000299977.9
SLFN5	NM_001330183.2 linkuse as main transcript	c.977G>A	p.Arg326Lys	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN5	ENST00000299977.9 linkuse as main transcript	c.977G>A	p.Arg326Lys	missense_variant	2/5	1	NM_144975.4	P1	Q08AF3-1
SLFN5	ENST00000592325.1 linkuse as main transcript	c.977G>A	p.Arg326Lys	missense_variant	2/2	1			Q08AF3-2
SLFN5	ENST00000542451.1 linkuse as main transcript	c.977G>A	p.Arg326Lys	missense_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000415

AC:

AN:

241192

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1448610

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000212

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.66

Cadd

Benign

0.36

Dann

Benign

0.44

DEOGEN2

Benign

0.0011

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.33

T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.3

N;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.89

N;N;.

REVEL

Benign

0.055

Sift

Benign

0.31

T;T;.

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.064

MutPred

0.34

Gain of ubiquitination at R326 (P = 0.0104);Gain of ubiquitination at R326 (P = 0.0104);Gain of ubiquitination at R326 (P = 0.0104);

MVP

0.36

MPC

0.066

ClinPred

0.016

GERP RS

-2.0

Varity_R

0.062

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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