Genetic Variant FYB1:p.Gly693Val (chr5-39122396-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001465.6(FYB1):c.2078G>T(p.Gly693Val) 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. 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. G693E) has been classified 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.02

Publications

0 publications found

Variant links:

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

FYB1 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23078468).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FYB1	NM_001465.6	MANE Select	c.2078G>T	p.Gly693Val	missense	Exon 14 of 19	NP_001456.3
FYB1	NM_001243093.2		c.2108G>T	p.Gly703Val	missense	Exon 14 of 19	NP_001230022.1	O15117-3
FYB1	NM_001349333.2		c.2078G>T	p.Gly693Val	missense	Exon 15 of 20	NP_001336262.1	O15117-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FYB1	ENST00000512982.4	TSL:2 MANE Select	c.2078G>T	p.Gly693Val	missense	Exon 14 of 19	ENSP00000425845.3	O15117-2
FYB1	ENST00000351578.12	TSL:1	c.1940G>T	p.Gly647Val	missense	Exon 13 of 18	ENSP00000316460.7	O15117-1
FYB1	ENST00000515010.5	TSL:1	c.1940G>T	p.Gly647Val	missense	Exon 12 of 17	ENSP00000426346.1	O15117-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702296

African (AFR)

AF:

0.00

AC:

AN:

32794

American (AMR)

AF:

0.00

AC:

AN:

39856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25386

East Asian (EAS)

AF:

0.00

AC:

AN:

38636

South Asian (SAS)

AF:

0.00

AC:

AN:

81172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083474

Other (OTH)

AF:

0.00

AC:

AN:

58734

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

M_CAP

Benign

0.040

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.95

PhyloP100

3.0

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.17

Sift

Uncertain

0.026

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.73

MutPred

0.19

Loss of loop (P = 0.1242)

MVP

0.55

ClinPred

0.98

GERP RS

4.9

Varity_R

0.21

gMVP

0.044

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over