6-111714405-G-A

Position:

• chr6-111714405-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_002037.5(FYN):​c.286C>T​(p.Arg96Trp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FYN NM_002037.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.36

Genes affected

FYN (HGNC:4037): (FYN proto-oncogene, Src family tyrosine kinase) This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816
• PP5: Variant 6-111714405-G-A is Pathogenic according to our data. Variant chr6-111714405-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2681289.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYN	NM_002037.5	c.286C>T	p.Arg96Trp	missense_variant	5/14	ENST00000354650.7	NP_002028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYN	ENST00000354650.7	c.286C>T	p.Arg96Trp	missense_variant	5/14	1	NM_002037.5	ENSP00000346671	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Pathogenic:1

Pathogenic, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	.;.;D;.;D;.;T;T;.;T;T;T;T;T;.;T;D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	D;.;.;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.038	T
MutationAssessor	Pathogenic	3.1	M;M;M;M;M;M;.;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	A;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.49
Sift	Benign	0.087	T;T;T;T;T;T;T;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.032	D;D;D;D;D;D;.;.;.;T;.;D;.;T;D;.;D
Polyphen		1.0, 0.83	.;.;D;P;D;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.75
MutPred		0.62		Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);Gain of catalytic residue at R96 (P = 0.0233);
MVP		0.90
MPC		2.4
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.57
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-112035608;