rs745672593

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001465.6(FYB1):​c.393G>T​(p.Trp131Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FYB1 NM_001465.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15802649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.393G>T	p.Trp131Cys	missense_variant	2/19	ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.393G>T	p.Trp131Cys	missense_variant	2/19	2	NM_001465.6	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249224 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135196

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.65
DEOGEN2	Benign	0.12	T;.;.;T;.;T
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.082
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.91	.;.;D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.77	N;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;.;.;N;N;D
REVEL	Benign	0.065
Sift	Uncertain	0.0090	D;.;.;D;D;D
Sift4G	Uncertain	0.051	T;.;D;T;T;.
Polyphen		0.76	P;.;.;P;.;.
Vest4		0.29
MutPred		0.14		Loss of glycosylation at T128 (P = 0.1354);.;.;Loss of glycosylation at T128 (P = 0.1354);Loss of glycosylation at T128 (P = 0.1354);Loss of glycosylation at T128 (P = 0.1354);
MVP		0.43
ClinPred		0.46	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.069

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

LitVar

Other links and lift over

dbSNP: rs745672593; hg19: chr5-39202670;