NM_001465.6:c.2311A>G

Variant names:

• chr5-39118964-T-C
• rs897807123
• NM_001465.6:c.2311A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001465.6(FYB1):​c.2311A>G​(p.Arg771Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,421,580 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000014 (0 hom.)
• Consequence: FYB1 NM_001465.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.21

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39770865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001465.6	c.2311A>G	p.Arg771Gly	missense_variant	Exon 16 of 19	ENST00000512982.4	NP_001456.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB1	ENST00000512982.4	c.2311A>G	p.Arg771Gly	missense_variant	Exon 16 of 19	2	NM_001465.6	ENSP00000425845.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1421580 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 706460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2311A>G (p.R771G) alteration is located in exon 1 (coding exon 1) of the FYB gene. This alteration results from a A to G substitution at nucleotide position 2311, causing the arginine (R) at amino acid position 771 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.;.;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;.;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.40	T;T;T;T;T
MetaSVM	Benign	-0.71	T
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.6	D;.;.;D;D
REVEL	Benign	0.15
Sift	Benign	0.033	D;.;.;D;T
Sift4G	Uncertain	0.010	D;.;D;D;D
Polyphen		0.93	P;.;.;P;.
Vest4		0.41
MutPred		0.34		Loss of MoRF binding (P = 0.0158);.;.;Loss of MoRF binding (P = 0.0158);.;
MVP		0.50
ClinPred		0.98	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs897807123; hg19: chr5-39119066;