rs10512472

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001129820.2(SLFN14):c.278A>G(p.Gln93Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,551,612 control chromosomes in the GnomAD database, including 28,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3002 hom., cov: 32)

Exomes 𝑓: 0.19 ( 25326 hom. )

Consequence

SLFN14
NM_001129820.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.11

Publications

47 publications found

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 Gene-Disease associations (from GenCC):

platelet-type bleeding disorder 20
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

SLFN14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037332773).

BP6

Variant 17-35557785-T-C is Benign according to our data. Variant chr17-35557785-T-C is described in ClinVar as Benign. ClinVar VariationId is 1333129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN14	NM_001129820.2 link	c.278A>G	p.Gln93Arg	missense_variant	Exon 3 of 6	ENST00000674182.1	NP_001123292.1	P0C7P3-1
SLFN14	XM_017024577.2 link	c.278A>G	p.Gln93Arg	missense_variant	Exon 3 of 6		XP_016880066.1	P0C7P3-1
SLFN14	XM_017024578.2 link	c.278A>G	p.Gln93Arg	missense_variant	Exon 2 of 5		XP_016880067.1	P0C7P3-1
SLFN14	XM_017024579.2 link	c.278A>G	p.Gln93Arg	missense_variant	Exon 2 of 5		XP_016880068.1	P0C7P3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN14	ENST00000674182.1 link	c.278A>G	p.Gln93Arg	missense_variant	Exon 3 of 6		NM_001129820.2	ENSP00000501524.1		P0C7P3-1
SLFN14	ENST00000415846.3 link	c.278A>G	p.Gln93Arg	missense_variant	Exon 1 of 4	1		ENSP00000391101.2		P0C7P3-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29840

AN:

152100

Hom.:

2995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.213

GnomAD2 exomes

AF:

0.209

AC:

32173

AN:

154038

AF XY:

0.208

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.186

AC:

260020

AN:

1399392

Hom.:

25326

Cov.:

AF XY:

0.187

AC XY:

128939

AN XY:

690206

show subpopulations

African (AFR)

AF:

0.203

AC:

6420

AN:

31598

American (AMR)

AF:

0.238

AC:

8497

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6126

AN:

25182

East Asian (EAS)

AF:

0.358

AC:

12789

AN:

35736

South Asian (SAS)

AF:

0.220

AC:

17448

AN:

79236

European-Finnish (FIN)

AF:

0.177

AC:

8743

AN:

49276

Middle Eastern (MID)

AF:

0.246

AC:

1402

AN:

5698

European-Non Finnish (NFE)

AF:

0.173

AC:

187057

AN:

1078962

Other (OTH)

AF:

0.199

AC:

11538

AN:

58000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

14034

28068

42101

56135

70169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6894

13788

20682

27576

34470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.196

AC:

29872

AN:

152220

Hom.:

3002

Cov.:

AF XY:

0.199

AC XY:

14826

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.206

AC:

8533

AN:

41518

American (AMR)

AF:

0.219

AC:

3345

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3472

East Asian (EAS)

AF:

0.340

AC:

1761

AN:

5186

South Asian (SAS)

AF:

0.226

AC:

1090

AN:

4830

European-Finnish (FIN)

AF:

0.185

AC:

1954

AN:

10584

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11698

AN:

68020

Other (OTH)

AF:

0.217

AC:

459

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1275

2550

3826

5101

6376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

12364

Bravo

AF:

0.203

TwinsUK

AF:

0.164

AC:

608

ALSPAC

AF:

0.178

AC:

686

ESP6500AA

AF:

0.208

AC:

288

ESP6500EA

AF:

0.173

AC:

549

ExAC

AF:

0.190

AC:

4205

Asia WGS

AF:

0.290

AC:

1011

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SLFN14-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Platelet-type bleeding disorder 20

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0035

Eigen

Benign

0.16

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.8

PhyloP100

3.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.058

Sift

Uncertain

0.014

Sift4G

Benign

0.24

Polyphen

0.80

Vest4

0.083

ClinPred

0.027

GERP RS

4.3

PromoterAI

0.033

Neutral

(source)

Varity_R

0.15

gMVP

0.16

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over