Variant chr17-35352709-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001376007.1(SLFN11):c.2353G>T(p.Val785Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 1,614,208 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00044 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

SLFN11
NM_001376007.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.93

Variant links:

Genes affected

SLFN11 (HGNC:26633): (schlafen family member 11) Enables tRNA binding activity. Involved in several processes, including defense response to virus; negative regulation of G1/S transition of mitotic cell cycle; and replication fork arrest. Located in cytosol; nucleoplasm; and site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]

SLFN11 links:

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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=0.00920403).

BP6

Variant 17-35352709-C-A is Benign according to our data. Variant chr17-35352709-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2217311.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLFN11	NM_001376007.1 linkuse as main transcript	c.2353G>T	p.Val785Leu	missense_variant	7/7	ENST00000685675.1	NP_001362936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLFN11	ENST00000685675.1 linkuse as main transcript	c.2353G>T	p.Val785Leu	missense_variant	7/7		NM_001376007.1	ENSP00000510787.1	Q7Z7L1
SLFN11	ENST00000308377.8 linkuse as main transcript	c.2353G>T	p.Val785Leu	missense_variant	5/5	1		ENSP00000312402.4	Q7Z7L1
SLFN11	ENST00000394566.5 linkuse as main transcript	c.2353G>T	p.Val785Leu	missense_variant	7/7	2		ENSP00000378067.1	Q7Z7L1
SLFN11	ENST00000592108.1 linkuse as main transcript	c.*162G>T		3_prime_UTR_variant	2/2	5		ENSP00000465198.1	K7EJJ3

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251402

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000457

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000258

AC:

377

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

197

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000216

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.000440

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000450

Hom.:

Bravo

AF:

0.000623

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000395

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000711

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

Jun 11, 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

0.12

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.0010

DANN

Benign

0.13

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.00092

LIST_S2

Benign

0.31

.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.0092

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.95

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.98

N;N

REVEL

Benign

0.22

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.025

MutPred

0.37

Loss of catalytic residue at V785 (P = 0.0522);Loss of catalytic residue at V785 (P = 0.0522);

MVP

0.18

MPC

0.026

ClinPred

0.021

GERP RS

-8.0

Varity_R

0.013

gMVP

0.13

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