NM_001129820.2:c.2489T>C

Variant names:

• chr17-35548489-A-G
• rs542195109
• NM_001129820.2:c.2489T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001129820.2(SLFN14):​c.2489T>C​(p.Leu830Pro) 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. 16/22 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. L830R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN14 NM_001129820.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054739356).

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.2489T>C	p.Leu830Pro	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.2489T>C	p.Leu830Pro	missense	Exon 6 of 6	ENSP00000501524.1	P0C7P3-1
	SLFN14	ENST00000415846.3	TSL:1	c.2489T>C	p.Leu830Pro	missense	Exon 4 of 4	ENSP00000391101.2	P0C7P3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.035
DANN	Benign	0.59
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.77	N
PhyloP100		-2.9
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.040
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.47		Loss of stability (P = 0.0097)
MVP		0.081
ClinPred		0.068	T
GERP RS		-6.6
Varity_R		0.054
gMVP		0.72

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: rs542195109; hg19: chr17-33875508;