chr17-35548265-G-A

Position:

• chr17-35548265-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001129820.2(SLFN14):​c.2713C>T​(p.Leu905Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,551,228 control chromosomes in the GnomAD database, including 2,424 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.069 (494 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1930 hom.)
• Consequence: SLFN14 NM_001129820.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.23

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015683174).
• BP6: Variant 17-35548265-G-A is Benign according to our data. Variant chr17-35548265-G-A is described in ClinVar as [Benign]. Clinvar id is 1239057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN14	NM_001129820.2	c.2713C>T	p.Leu905Phe	missense_variant	6/6	ENST00000674182.1
SLFN14	XM_017024577.2	c.2713C>T	p.Leu905Phe	missense_variant	6/6
SLFN14	XM_017024578.2	c.2713C>T	p.Leu905Phe	missense_variant	5/5
SLFN14	XM_017024579.2	c.2713C>T	p.Leu905Phe	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN14	ENST00000674182.1	c.2713C>T	p.Leu905Phe	missense_variant	6/6		NM_001129820.2	P1
SLFN14	ENST00000415846.3	c.2713C>T	p.Leu905Phe	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10476 AN: 152112 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0502

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0870

GnomAD3 exomes AF: 0.0458 AC: 7047 AN: 153812 Hom.: 229 AF XY: 0.0447 AC XY: 3647 AN XY: 81630

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0324

Gnomad ASJ exome AF: 0.0912

Gnomad EAS exome AF: 0.000275

Gnomad SAS exome AF: 0.0305

Gnomad FIN exome AF: 0.0284

Gnomad NFE exome AF: 0.0513

Gnomad OTH exome AF: 0.0595

GnomAD4 exome AF: 0.0475 AC: 66458 AN: 1398998 Hom.: 1930 Cov.: 33 AF XY: 0.0467 AC XY: 32246 AN XY: 689992

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0362

Gnomad4 ASJ exome AF: 0.0891

Gnomad4 EAS exome AF: 0.000224

Gnomad4 SAS exome AF: 0.0316

Gnomad4 FIN exome AF: 0.0274

Gnomad4 NFE exome AF: 0.0471

Gnomad4 OTH exome AF: 0.0553

GnomAD4 genome AF: 0.0690 AC: 10499 AN: 152230 Hom.: 494 Cov.: 32 AF XY: 0.0665 AC XY: 4950 AN XY: 74430

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0501

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.0296

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.0875

Alfa AF: 0.0579 Hom.: 395

Bravo AF: 0.0728

TwinsUK AF: 0.0458 AC: 170

ALSPAC AF: 0.0516 AC: 199

ESP6500AA AF: 0.131 AC: 181

ESP6500EA AF: 0.0519 AC: 165

ExAC AF: 0.0518 AC: 1124

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2019	- -

Platelet-type bleeding disorder 20 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.023
Sift	Benign	0.21	T
Sift4G	Uncertain	0.042	D
Polyphen		0.053	B
Vest4		0.042
ClinPred		0.0074	T
GERP RS		3.4
Varity_R		0.098
gMVP		0.27

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

Other links and lift over

dbSNP: rs9907259; hg19: chr17-33875284;