Variant 17-35548243-T-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.2735A>T(p.Tyr912Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,548,762 control chromosomes in the GnomAD database, including 74,475 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.34 ( 9270 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65205 hom. )

Consequence

SLFN14
NM_001129820.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.746

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=0.0021972358).

BP6

Variant 17-35548243-T-A is Benign according to our data. Variant chr17-35548243-T-A is described in ClinVar as [Benign]. Clinvar id is 1245977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLFN14	NM_001129820.2 linkuse as main transcript	c.2735A>T	p.Tyr912Phe	missense_variant	6/6	ENST00000674182.1
SLFN14	XM_017024577.2 linkuse as main transcript	c.2735A>T	p.Tyr912Phe	missense_variant	6/6
SLFN14	XM_017024578.2 linkuse as main transcript	c.2735A>T	p.Tyr912Phe	missense_variant	5/5
SLFN14	XM_017024579.2 linkuse as main transcript	c.2735A>T	p.Tyr912Phe	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN14	ENST00000674182.1 linkuse as main transcript	c.2735A>T	p.Tyr912Phe	missense_variant	6/6		NM_001129820.2	P1	P0C7P3-1
SLFN14	ENST00000415846.3 linkuse as main transcript	c.2735A>T	p.Tyr912Phe	missense_variant	4/4	1		P1	P0C7P3-1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51312

AN:

151978

Hom.:

9248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.348

GnomAD3 exomes

AF:

0.315

AC:

48301

AN:

153136

Hom.:

8008

AF XY:

0.319

AC XY:

25960

AN XY:

81298

show subpopulations

Gnomad AFR exome

AF:

0.450

Gnomad AMR exome

AF:

0.300

Gnomad ASJ exome

AF:

0.411

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.300

AC:

419536

AN:

1396666

Hom.:

65205

Cov.:

AF XY:

0.303

AC XY:

208349

AN XY:

688614

show subpopulations

Gnomad4 AFR exome

AF:

0.458

Gnomad4 AMR exome

AF:

0.298

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.338

AC:

51396

AN:

152096

Hom.:

9270

Cov.:

AF XY:

0.334

AC XY:

24834

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.456

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.393

Gnomad4 FIN

AF:

0.242

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.348

Alfa

AF:

0.312

Hom.:

6011

Bravo

AF:

0.347

TwinsUK

AF:

0.292

AC:

1083

ALSPAC

AF:

0.309

AC:

1192

ESP6500AA

AF:

0.452

AC:

626

ESP6500EA

AF:

0.301

AC:

958

ExAC

AF:

0.338

AC:

7220

Asia WGS

AF:

0.315

AC:

1097

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

0.054

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.9

DANN

Benign

0.12

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00035

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

0.46

REVEL

Benign

0.011

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.028

ClinPred

0.00029

GERP RS

2.8

Varity_R

0.060

gMVP

0.089

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