Variant 17-35259394-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144975.4(SLFN5):c.704C>T(p.Thr235Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SLFN5
NM_144975.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.185

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05851388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN5	NM_144975.4 linkuse as main transcript	c.704C>T	p.Thr235Ile	missense_variant	2/5	ENST00000299977.9
SLFN5	NM_001330183.2 linkuse as main transcript	c.704C>T	p.Thr235Ile	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN5	ENST00000299977.9 linkuse as main transcript	c.704C>T	p.Thr235Ile	missense_variant	2/5	1	NM_144975.4	P1	Q08AF3-1
SLFN5	ENST00000592325.1 linkuse as main transcript	c.704C>T	p.Thr235Ile	missense_variant	2/2	1			Q08AF3-2
SLFN5	ENST00000542451.1 linkuse as main transcript	c.704C>T	p.Thr235Ile	missense_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251228

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.000615

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:

0.0000103

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00

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:

0.00

GnomAD4 genome

AF:

0.000230

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.0000654

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:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

The c.704C>T (p.T235I) alteration is located in exon 2 (coding exon 1) of the SLFN5 gene. This alteration results from a C to T substitution at nucleotide position 704, causing the threonine (T) at amino acid position 235 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.075

T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.7

D;D;.

REVEL

Benign

0.088

Sift

Uncertain

0.0040

D;D;.

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.32

MVP

0.35

MPC

0.34

ClinPred

0.17

GERP RS

1.5

Varity_R

0.25

gMVP

0.23

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

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