Variant 17-35548762-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001129820.2(SLFN14):c.2216C>T(p.Ala739Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,551,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLFN14
NM_001129820.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19550002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLFN14	NM_001129820.2 linkuse as main transcript	c.2216C>T	p.Ala739Val	missense_variant	6/6	ENST00000674182.1
SLFN14	XM_017024577.2 linkuse as main transcript	c.2216C>T	p.Ala739Val	missense_variant	6/6
SLFN14	XM_017024578.2 linkuse as main transcript	c.2216C>T	p.Ala739Val	missense_variant	5/5
SLFN14	XM_017024579.2 linkuse as main transcript	c.2216C>T	p.Ala739Val	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN14	ENST00000674182.1 linkuse as main transcript	c.2216C>T	p.Ala739Val	missense_variant	6/6		NM_001129820.2	P1	P0C7P3-1
SLFN14	ENST00000415846.3 linkuse as main transcript	c.2216C>T	p.Ala739Val	missense_variant	4/4	1		P1	P0C7P3-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152102

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:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000325

AC:

AN:

153902

Hom.:

AF XY:

0.0000367

AC XY:

AN XY:

81656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1399376

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

690196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.0000874

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 23, 2021

The c.2216C>T (p.A739V) alteration is located in exon 4 (coding exon 4) of the SLFN14 gene. This alteration results from a C to T substitution at nucleotide position 2216, causing the alanine (A) at amino acid position 739 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

M_CAP

Benign

0.015

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.94

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.098

Sift

Benign

0.064

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.52

MutPred

0.26

Loss of disorder (P = 0.0691);

MVP

0.12

ClinPred

0.45

GERP RS

5.4

Varity_R

0.15

gMVP

0.32

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