6-111694644-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002037.5(FYN):​c.1103T>C​(p.Val368Ala) variant causes a missense change involving the alteration of a 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FYN
NM_002037.5 missense

Scores

13
4
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.16
Variant links:
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]

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ACMG classification

Classification made for transcript

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, 0.907

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FYNNM_002037.5 linkuse as main transcriptc.1103T>C p.Val368Ala missense_variant 11/14 ENST00000354650.7 NP_002028.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FYNENST00000354650.7 linkuse as main transcriptc.1103T>C p.Val368Ala missense_variant 11/141 NM_002037.5 ENSP00000346671 P3P06241-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2023The c.1103T>C (p.V368A) alteration is located in exon 1 (coding exon 1) of the FYN gene. This alteration results from a T to C substitution at nucleotide position 1103, causing the valine (V) at amino acid position 368 to be replaced by an alanine (A). 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
0.95
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.89
.;.;D;.;D;.
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.90
D;.;.;T;D;.
M_CAP
Uncertain
0.13
D
MetaRNN
Pathogenic
0.91
D;D;D;D;D;D
MetaSVM
Uncertain
0.18
D
MutationAssessor
Benign
0.59
.;.;N;.;N;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-3.7
D;D;D;D;D;D
REVEL
Pathogenic
0.79
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D
Polyphen
1.0, 0.99
.;.;D;D;D;.
Vest4
0.70
MutPred
0.81
.;.;Loss of stability (P = 0.0439);.;Loss of stability (P = 0.0439);.;
MVP
0.97
MPC
2.6
ClinPred
0.99
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.92
gMVP
0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-112015847; API