rs869320714

Variant names:

• chr17-35557404-A-G
• rs869320714
• NM_001129820.2:c.659T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-35557404-A-G
• chr17-35557404-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM2 PM5 BP4_Strong

The NM_001129820.2(SLFN14):​c.659T>C​(p.Val220Ala) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V220D) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN14 NM_001129820.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 0 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-35557404-A-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 225533.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.06426978).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN14	NM_001129820.2	MANE Select	c.659T>C	p.Val220Ala	missense	Exon 3 of 6	NP_001123292.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN14	ENST00000674182.1	MANE Select	c.659T>C	p.Val220Ala	missense	Exon 3 of 6	ENSP00000501524.1
	SLFN14	ENST00000415846.3	TSL:1	c.659T>C	p.Val220Ala	missense	Exon 1 of 4	ENSP00000391101.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.9
DANN	Benign	0.88
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.0
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.096
Sift	Benign	0.17	T
Sift4G	Benign	0.12	T
Polyphen		0.17	B
Vest4		0.20
MutPred		0.39		Loss of helix (P = 0.0376)
MVP		0.048
ClinPred		0.20	T
GERP RS		4.6
Varity_R		0.11
gMVP		0.57

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: rs869320714; hg19: chr17-33884423;