Variant chr17-35548805-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001129820.2(SLFN14):c.2173C>T(p.Arg725*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,551,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

SLFN14
NM_001129820.2 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.389

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLFN14	NM_001129820.2 linkuse as main transcript	c.2173C>T	p.Arg725*	stop_gained	6/6	ENST00000674182.1	NP_001123292.1	P0C7P3-1
SLFN14	XM_017024577.2 linkuse as main transcript	c.2173C>T	p.Arg725*	stop_gained	6/6		XP_016880066.1	P0C7P3-1
SLFN14	XM_017024578.2 linkuse as main transcript	c.2173C>T	p.Arg725*	stop_gained	5/5		XP_016880067.1	P0C7P3-1
SLFN14	XM_017024579.2 linkuse as main transcript	c.2173C>T	p.Arg725*	stop_gained	5/5		XP_016880068.1	P0C7P3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLFN14	ENST00000674182.1 linkuse as main transcript	c.2173C>T	p.Arg725*	stop_gained	6/6		NM_001129820.2	ENSP00000501524.1		P0C7P3-1
SLFN14	ENST00000415846.3 linkuse as main transcript	c.2173C>T	p.Arg725*	stop_gained	4/4	1		ENSP00000391101.2		P0C7P3-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000650

AC:

AN:

153894

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000715

AC:

AN:

1399392

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

690206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000649

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Platelet-type bleeding disorder 20

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Benign

0.078

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.12

Vest4

0.32

GERP RS

2.0

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