rs3756772

Positions:

• chr6-116003979-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000606080.2(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. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.38 (12324 hom., cov: 32)
  • Exomes 𝑓: 0.42 (135703 hom.)
• Consequence: FRK ENST00000606080.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FRK	NM_002031.3	c.364G>A	p.Gly122Arg	missense_variant	2/8	ENST00000606080.2	NP_002022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRK	ENST00000606080.2	c.364G>A	p.Gly122Arg	missense_variant	2/8	1	NM_002031.3	ENSP00000476145	P1
	ENST00000692859.2	n.222+96513G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58135 AN: 151866 Hom.: 12319 Cov.: 32

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

GnomAD3 exomes AF: 0.456 AC: 114228 AN: 250442 Hom.: 28084 AF XY: 0.462 AC XY: 62519 AN XY: 135442

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 SAS exome AF: 0.553

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.: 32 AF XY: 0.428 AC XY: 310183 AN XY: 725234

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.748

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.383 AC: 58160 AN: 151984 Hom.: 12324 Cov.: 32 AF XY: 0.388 AC XY: 28821 AN XY: 74272

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.392

Alfa AF: 0.421 Hom.: 35701

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	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.000018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.39	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.044
MutPred		0.10		Gain of phosphorylation at S124 (P = 0.0736);
MPC		0.22
ClinPred		0.0082	T
GERP RS		4.8
Varity_R		0.079
gMVP		0.51

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

Other links and lift over

dbSNP: rs3756772; hg19: chr6-116325142; COSMIC: COSV73383915;