6-115968722-C-A

Variant summary

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

The NM_002031.3(FRK):​c.484G>T​(p.Val162Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,612,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V162I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

FRK
NM_002031.3 missense

Scores

4
10
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.14
Variant links:
Genes affected
FRK (HGNC:3955): (fyn related Src family tyrosine kinase) The protein encoded by this gene belongs to the TYR family of protein kinases. This tyrosine kinase is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. [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, 0.813
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRKNM_002031.3 linkc.484G>T p.Val162Leu missense_variant Exon 3 of 8 ENST00000606080.2 NP_002022.1 P42685-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRKENST00000606080.2 linkc.484G>T p.Val162Leu missense_variant Exon 3 of 8 1 NM_002031.3 ENSP00000476145.1 P42685-1
ENSG00000289376ENST00000692859.2 linkn.223-66544G>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000799
AC:
20
AN:
250344
Hom.:
0
AF XY:
0.0000887
AC XY:
12
AN XY:
135234
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000602
AC:
88
AN:
1460610
Hom.:
0
Cov.:
30
AF XY:
0.0000619
AC XY:
45
AN XY:
726496
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.0000675
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000613
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Uncertain
0.060
T
BayesDel_noAF
Uncertain
0.090
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Uncertain
0.53
D
MutationAssessor
Pathogenic
3.5
H
PrimateAI
Uncertain
0.57
T
Sift4G
Uncertain
0.013
D
Polyphen
0.24
B
Vest4
0.86
MutPred
0.71
Loss of methylation at K163 (P = 0.0384);
MVP
0.41
MPC
0.27
ClinPred
0.57
D
GERP RS
6.0
Varity_R
0.91
gMVP
0.70

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: rs764595423; hg19: chr6-116289885; API