chr6-111707998-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_002037.5(FYN):​c.367C>T​(p.Arg123Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,480 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FYN
NM_002037.5 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.835
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FYNNM_002037.5 linkuse as main transcriptc.367C>T p.Arg123Cys missense_variant 6/14 ENST00000354650.7 NP_002028.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FYNENST00000354650.7 linkuse as main transcriptc.367C>T p.Arg123Cys missense_variant 6/141 NM_002037.5 ENSP00000346671 P3P06241-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251276
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135806
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461480
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727108
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMay 04, 2022The c.367C>T (p.R123C) alteration is located in exon 1 (coding exon 1) of the FYN gene. This alteration results from a C to T substitution at nucleotide position 367, causing the arginine (R) at amino acid position 123 to be replaced by a cysteine (C). 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
Benign
0.32
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.53
.;.;D;.;D;.;T;T;.;T;T;T;T
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D;.;.;D;D;.;D;D;D;D;D;D;D
M_CAP
Benign
0.036
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.4
M;M;M;M;M;M;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-5.0
D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.017
D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.014
D;D;D;D;D;D;.;.;.;D;.;D;.
Polyphen
1.0
.;.;D;D;D;.;.;.;.;.;.;.;.
Vest4
0.68
MutPred
0.58
Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);
MVP
0.91
MPC
2.7
ClinPred
0.99
D
GERP RS
6.2
Varity_R
0.88
gMVP
0.77

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766363948; hg19: chr6-112029201; API