Variant rs757188030 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001129820.2(SLFN14):c.667C>T(p.Arg223Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,551,508 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SLFN14
NM_001129820.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.201

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-35557396-G-A is Pathogenic according to our data. Variant chr17-35557396-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 225536.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLFN14	NM_001129820.2 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	3/6	ENST00000674182.1	NP_001123292.1
SLFN14	XM_017024577.2 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	3/6		XP_016880066.1
SLFN14	XM_017024578.2 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	2/5		XP_016880067.1
SLFN14	XM_017024579.2 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	2/5		XP_016880068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLFN14	ENST00000674182.1 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	3/6		NM_001129820.2	ENSP00000501524	P1	P0C7P3-1
SLFN14	ENST00000415846.3 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	1/4	1		ENSP00000391101	P1	P0C7P3-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000650

AC:

AN:

153960

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000406

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:

0.00000429

AC:

AN:

1399384

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000452

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Platelet-type bleeding disorder 20

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Benign

0.12

Eigen_PC

Benign

-0.053

FATHMM_MKL

Benign

0.080

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

0.99

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.34

Sift

Benign

0.12

Sift4G

Benign

0.061

Polyphen

1.0

Vest4

0.81

MutPred

0.49

Gain of catalytic residue at R223 (P = 0.0565);

MVP

0.40

ClinPred

0.73

GERP RS

1.1

Varity_R

0.064

gMVP

0.65

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