Variant 17-35548687-A-G 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.2291T>C(p.Leu764Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,399,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SLFN14
NM_001129820.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.379

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07979995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLFN14	NM_001129820.2 linkuse as main transcript	c.2291T>C	p.Leu764Ser	missense_variant	6/6	ENST00000674182.1
SLFN14	XM_017024577.2 linkuse as main transcript	c.2291T>C	p.Leu764Ser	missense_variant	6/6
SLFN14	XM_017024578.2 linkuse as main transcript	c.2291T>C	p.Leu764Ser	missense_variant	5/5
SLFN14	XM_017024579.2 linkuse as main transcript	c.2291T>C	p.Leu764Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN14	ENST00000674182.1 linkuse as main transcript	c.2291T>C	p.Leu764Ser	missense_variant	6/6		NM_001129820.2	P1	P0C7P3-1
SLFN14	ENST00000415846.3 linkuse as main transcript	c.2291T>C	p.Leu764Ser	missense_variant	4/4	1		P1	P0C7P3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

153832

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81610

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000336

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1399388

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

690204

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000232

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 12, 2024

The c.2291T>C (p.L764S) alteration is located in exon 4 (coding exon 4) of the SLFN14 gene. This alteration results from a T to C substitution at nucleotide position 2291, causing the leucine (L) at amino acid position 764 to be replaced by a serine (S). 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

0.095

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.2

DANN

Benign

0.96

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.41

M_CAP

Benign

0.0051

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.020

Sift

Benign

0.050

Sift4G

Uncertain

0.057

Polyphen

0.11

Vest4

0.17

MutPred

0.46

Loss of sheet (P = 0.0142);

MVP

0.12

ClinPred

0.074

GERP RS

3.1

Varity_R

0.092

gMVP

0.29

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