Variant 17-35548265-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001129820.2(SLFN14):c.2713C>T(p.Leu905Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,551,228 control chromosomes in the GnomAD database, including 2,424 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.069 ( 494 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1930 hom. )

Consequence

SLFN14
NM_001129820.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

SLFN14 (HGNC:32689): (schlafen family member 14) The protein encoded by this gene plays an important role in platelet formation and function. Defects in this gene are a cause of thrombocytopenia with excessive bleeding. [provided by RefSeq, Jul 2016]

SLFN14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015683174).

BP6

Variant 17-35548265-G-A is Benign according to our data. Variant chr17-35548265-G-A is described in ClinVar as [Benign]. Clinvar id is 1239057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLFN14	NM_001129820.2 linkuse as main transcript	c.2713C>T	p.Leu905Phe	missense_variant	6/6	ENST00000674182.1
SLFN14	XM_017024577.2 linkuse as main transcript	c.2713C>T	p.Leu905Phe	missense_variant	6/6
SLFN14	XM_017024578.2 linkuse as main transcript	c.2713C>T	p.Leu905Phe	missense_variant	5/5
SLFN14	XM_017024579.2 linkuse as main transcript	c.2713C>T	p.Leu905Phe	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN14	ENST00000674182.1 linkuse as main transcript	c.2713C>T	p.Leu905Phe	missense_variant	6/6		NM_001129820.2	P1	P0C7P3-1
SLFN14	ENST00000415846.3 linkuse as main transcript	c.2713C>T	p.Leu905Phe	missense_variant	4/4	1		P1	P0C7P3-1

Frequencies

GnomAD3 genomes

AF:

0.0689

AC:

10476

AN:

152112

Hom.:

493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0502

Gnomad ASJ

AF:

0.0879

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.0296

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0469

Gnomad OTH

AF:

0.0870

GnomAD3 exomes

AF:

0.0458

AC:

7047

AN:

153812

Hom.:

229

AF XY:

0.0447

AC XY:

3647

AN XY:

81630

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0324

Gnomad ASJ exome

AF:

0.0912

Gnomad EAS exome

AF:

0.000275

Gnomad SAS exome

AF:

0.0305

Gnomad FIN exome

AF:

0.0284

Gnomad NFE exome

AF:

0.0513

Gnomad OTH exome

AF:

0.0595

GnomAD4 exome

AF:

0.0475

AC:

66458

AN:

1398998

Hom.:

1930

Cov.:

AF XY:

0.0467

AC XY:

32246

AN XY:

689992

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.0362

Gnomad4 ASJ exome

AF:

0.0891

Gnomad4 EAS exome

AF:

0.000224

Gnomad4 SAS exome

AF:

0.0316

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0471

Gnomad4 OTH exome

AF:

0.0553

GnomAD4 genome

AF:

0.0690

AC:

10499

AN:

152230

Hom.:

494

Cov.:

AF XY:

0.0665

AC XY:

4950

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0501

Gnomad4 ASJ

AF:

0.0879

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0309

Gnomad4 FIN

AF:

0.0296

Gnomad4 NFE

AF:

0.0469

Gnomad4 OTH

AF:

0.0875

Alfa

AF:

0.0579

Hom.:

395

Bravo

AF:

0.0728

TwinsUK

AF:

0.0458

AC:

170

ALSPAC

AF:

0.0516

AC:

199

ESP6500AA

AF:

0.131

AC:

181

ESP6500EA

AF:

0.0519

AC:

165

ExAC

AF:

0.0518

AC:

1124

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 05, 2019

- -

Platelet-type bleeding disorder 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.063

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

REVEL

Benign

0.023

Sift

Benign

0.21

Sift4G

Uncertain

0.042

Polyphen

0.053

Vest4

0.042

ClinPred

0.0074

GERP RS

3.4

Varity_R

0.098

gMVP

0.27

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