rs745672593

Variant names:

• chr5-39202568-C-T
• rs745672593
• NM_001465.6:c.393G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-39202568-C-T
• chr5-39202568-C-A
• chr5-39202568-C-G

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001465.6(FYB1):​c.393G>A​(p.Trp131*) variant causes a stop gained 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FYB1 NM_001465.6 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.639
• Publications: 2 publications found

Genes affected

FYB1 (HGNC:4036): (FYN binding protein 1) The protein encoded by this gene is an adapter for the FYN protein and LCP2 signaling cascades in T-cells. The encoded protein is involved in platelet activation and controls the expression of interleukin-2. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

FYB1 Gene-Disease associations (from GenCC):

• thrombocytopenia 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-39202568-C-T is Pathogenic according to our data. Variant chr5-39202568-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 417971.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001465.6. 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
	FYB1	NM_001465.6	MANE Select	c.393G>A	p.Trp131*	stop_gained	Exon 2 of 19	NP_001456.3
	FYB1	NM_001243093.2		c.423G>A	p.Trp141*	stop_gained	Exon 2 of 19	NP_001230022.1	O15117-3
	FYB1	NM_001349333.2		c.393G>A	p.Trp131*	stop_gained	Exon 3 of 20	NP_001336262.1	O15117-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	ENST00000512982.4	TSL:2 MANE Select	c.393G>A	p.Trp131*	stop_gained	Exon 2 of 19	ENSP00000425845.3	O15117-2
	FYB1	ENST00000351578.12	TSL:1	c.393G>A	p.Trp131*	stop_gained	Exon 2 of 18	ENSP00000316460.7	O15117-1
	FYB1	ENST00000515010.5	TSL:1	c.393G>A	p.Trp131*	stop_gained	Exon 1 of 17	ENSP00000426346.1	O15117-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Thrombocytopenia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.45	N
PhyloP100		0.64
Vest4		0.83
GERP RS		4.4
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs745672593; hg19: chr5-39202670;