dbSNP rs3756772: FRK:p.Gly122Arg (chr6-116003979-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002031.3(FRK):c.364G>A(p.Gly122Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,609,432 control chromosomes in the GnomAD database, including 148,027 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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: 𝑓 0.38 ( 12324 hom., cov: 32)

Exomes 𝑓: 0.42 ( 135703 hom. )

Consequence

FRK
NM_002031.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Publications

45 publications found

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]

FRK links:

ENSG00000289376 (HGNC:):

ENSG00000289376 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7757095E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRK	NM_002031.3 link	c.364G>A	p.Gly122Arg	missense_variant	Exon 2 of 8	ENST00000606080.2	NP_002022.1	P42685-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRK	ENST00000606080.2 link	c.364G>A	p.Gly122Arg	missense_variant	Exon 2 of 8	1	NM_002031.3	ENSP00000476145.1		P42685-1
ENSG00000289376	ENST00000692859.3 link	n.268+96513G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58135

AN:

151866

Hom.:

12319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.661

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.391

GnomAD2 exomes

AF:

0.456

AC:

114228

AN:

250442

AF XY:

0.462

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.803

Gnomad FIN exome

AF:

0.423

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.423

AC:

616795

AN:

1457448

Hom.:

135703

Cov.:

AF XY:

0.428

AC XY:

310183

AN XY:

725234

show subpopulations

African (AFR)

AF:

0.201

AC:

6720

AN:

33418

American (AMR)

AF:

0.453

AC:

20250

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9224

AN:

26076

East Asian (EAS)

AF:

0.748

AC:

29614

AN:

39604

South Asian (SAS)

AF:

0.558

AC:

48008

AN:

86086

European-Finnish (FIN)

AF:

0.422

AC:

22428

AN:

53136

Middle Eastern (MID)

AF:

0.420

AC:

2417

AN:

5752

European-Non Finnish (NFE)

AF:

0.409

AC:

453045

AN:

1108440

Other (OTH)

AF:

0.416

AC:

25089

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15258

30516

45775

61033

76291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13906

27812

41718

55624

69530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.383

AC:

58160

AN:

151984

Hom.:

12324

Cov.:

AF XY:

0.388

AC XY:

28821

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.217

AC:

8997

AN:

41488

American (AMR)

AF:

0.431

AC:

6588

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1219

AN:

3470

East Asian (EAS)

AF:

0.786

AC:

4063

AN:

5168

South Asian (SAS)

AF:

0.556

AC:

2675

AN:

4812

European-Finnish (FIN)

AF:

0.424

AC:

4475

AN:

10544

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28595

AN:

67926

Other (OTH)

AF:

0.392

AC:

824

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1726

3452

5178

6904

8630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.415

Hom.:

66703

Bravo

AF:

0.374

TwinsUK

AF:

0.412

AC:

1527

ALSPAC

AF:

0.400

AC:

1541

ESP6500AA

AF:

0.218

AC:

960

ESP6500EA

AF:

0.415

AC:

3564

ExAC

AF:

0.455

AC:

55211

Asia WGS

AF:

0.569

AC:

1980

AN:

3476

EpiCase

AF:

0.416

EpiControl

AF:

0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.23

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.57

MetaRNN

Benign

0.000018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.28

PhyloP100

2.0

PrimateAI

Benign

0.39

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.044

MutPred

0.10

Gain of phosphorylation at S124 (P = 0.0736);

MPC

0.22

ClinPred

0.0082

GERP RS

4.8

Varity_R

0.079

gMVP

0.51

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over