17-35548471-A-AT

Variant names:

• chr17-35548471-A-AT
• NM_001129820.2:c.2506dupA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001129820.2(SLFN14):​c.2506dupA​(p.Met836AsnfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN14 NM_001129820.2 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.287

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN14	NM_001129820.2	c.2506dupA	p.Met836AsnfsTer5	frameshift_variant	Exon 6 of 6	ENST00000674182.1	NP_001123292.1
SLFN14	XM_017024577.2	c.2506dupA	p.Met836AsnfsTer5	frameshift_variant	Exon 6 of 6		XP_016880066.1
SLFN14	XM_017024578.2	c.2506dupA	p.Met836AsnfsTer5	frameshift_variant	Exon 5 of 5		XP_016880067.1
SLFN14	XM_017024579.2	c.2506dupA	p.Met836AsnfsTer5	frameshift_variant	Exon 5 of 5		XP_016880068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN14	ENST00000674182.1	c.2506dupA	p.Met836AsnfsTer5	frameshift_variant	Exon 6 of 6		NM_001129820.2	ENSP00000501524.1
SLFN14	ENST00000415846.3	c.2506dupA	p.Met836AsnfsTer5	frameshift_variant	Exon 4 of 4	1		ENSP00000391101.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 02, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Frameshift variant predicted to result in protein truncation, as the last 77 amino acids are replaced with 4 different amino acids in a gene for which loss-of-function is not a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33875490;