17-35548265-G-A

Variant names:

• chr17-35548265-G-A
• rs9907259
• NM_001129820.2:c.2713C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 20

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129820.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN14	NM_001129820.2	MANE Select	c.2713C>T	p.Leu905Phe	missense	Exon 6 of 6	NP_001123292.1	P0C7P3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN14	ENST00000674182.1	MANE Select	c.2713C>T	p.Leu905Phe	missense	Exon 6 of 6	ENSP00000501524.1	P0C7P3-1
	SLFN14	ENST00000415846.3	TSL:1	c.2713C>T	p.Leu905Phe	missense	Exon 4 of 4	ENSP00000391101.2	P0C7P3-1

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

GnomAD2 exomes AF: 0.0458 AC: 7047 AN: 153812 AF XY: 0.0447

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 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

African (AFR) AF: 0.138 AC: 4371 AN: 31570

American (AMR) AF: 0.0362 AC: 1291 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 2244 AN: 25178

East Asian (EAS) AF: 0.000224 AC: 8 AN: 35732

South Asian (SAS) AF: 0.0316 AC: 2507 AN: 79226

European-Finnish (FIN) AF: 0.0274 AC: 1347 AN: 49246

Middle Eastern (MID) AF: 0.119 AC: 675 AN: 5692

European-Non Finnish (NFE) AF: 0.0471 AC: 50810 AN: 1078702

Other (OTH) AF: 0.0553 AC: 3205 AN: 57984

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

African (AFR) AF: 0.134 AC: 5553 AN: 41528

American (AMR) AF: 0.0501 AC: 765 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4826

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10602

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0469 AC: 3191 AN: 68012

Other (OTH) AF: 0.0875 AC: 185 AN: 2114

Alfa AF: 0.0633 Hom.: 637

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Platelet-type bleeding disorder 20 (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.2
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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9907259; hg19: chr17-33875284; COSMIC: COSV107518895; COSMIC: COSV107518895;