chr5-39108243-C-T

Variant names:

• chr5-39108243-C-T
• NM_001465.6:c.2455G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001465.6(FYB1):​c.2455G>A​(p.Asp819Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FYB1 NM_001465.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40909886).

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.2455G>A	p.Asp819Asn	missense	Exon 18 of 19	NP_001456.3
	FYB1	NM_001243093.2		c.2485G>A	p.Asp829Asn	missense	Exon 18 of 19	NP_001230022.1	O15117-3
	FYB1	NM_001349333.2		c.2455G>A	p.Asp819Asn	missense	Exon 19 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.2455G>A	p.Asp819Asn	missense	Exon 18 of 19	ENSP00000425845.3	O15117-2
	FYB1	ENST00000351578.12	TSL:1	c.2317G>A	p.Asp773Asn	missense	Exon 17 of 18	ENSP00000316460.7	O15117-1
	FYB1	ENST00000515010.5	TSL:1	c.2317G>A	p.Asp773Asn	missense	Exon 16 of 17	ENSP00000426346.1	O15117-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1375232 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 678636

African (AFR) AF: 0.00 AC: 0 AN: 31080

American (AMR) AF: 0.00 AC: 0 AN: 35070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24540

East Asian (EAS) AF: 0.00 AC: 0 AN: 35302

South Asian (SAS) AF: 0.00 AC: 0 AN: 78042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060244

Other (OTH) AF: 0.00 AC: 0 AN: 56844

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.41	T
PhyloP100		3.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.64		Loss of helix (P = 0.1706)
MVP		0.71
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.54
gMVP		0.57
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr5-39108345;