rs869320714

chr17-35557404-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001129820.2(SLFN14):c.659T>A(p.Val220Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN14 NM_001129820.2 missense
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:3
• Conservation: PhyloP100: 2.03

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747
• PP5: Variant 17-35557404-A-T is Pathogenic according to our data. Variant chr17-35557404-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225533.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN14	NM_001129820.2	c.659T>A	p.Val220Asp	missense_variant	3/6	ENST00000674182.1
SLFN14	XM_017024577.2	c.659T>A	p.Val220Asp	missense_variant	3/6
SLFN14	XM_017024578.2	c.659T>A	p.Val220Asp	missense_variant	2/5
SLFN14	XM_017024579.2	c.659T>A	p.Val220Asp	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN14	ENST00000674182.1	c.659T>A	p.Val220Asp	missense_variant	3/6		NM_001129820.2	P1
SLFN14	ENST00000415846.3	c.659T>A	p.Val220Asp	missense_variant	1/4	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:3

Revision: no assertion criteria provided

Submissions by phenotype

Platelet-type bleeding disorder 20 Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 02, 2023	- -
Likely pathogenic, no assertion criteria provided	research	ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	-	- -

Thrombocytopenia;C1458140:Abnormal bleeding Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

NIHR Bioresource Rare Diseases, University of Cambridge

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.98	N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.77	P
Vest4		0.84
MutPred		0.59		Gain of disorder (P = 0.0133);
MVP		0.31
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.77
gMVP		0.87

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: rs869320714; hg19: chr17-33884423;