chr15-90889880-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002005.4(FES):c.967A>G(p.Met323Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,613,452 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M323L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.014 ( 64 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 62 hom. )

Consequence

FES
NM_002005.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.561

Publications

8 publications found

Variant links:

Genes affected

FES (HGNC:3657): (FES proto-oncogene, tyrosine kinase) This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. The gene product has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia but it is also involved in normal hematopoiesis as well as growth factor and cytokine receptor signaling. Alternative splicing results in multiple variants encoding different isoforms.[provided by RefSeq, Jan 2009]

FES links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021565259).

BP6

Variant 15-90889880-A-G is Benign according to our data. Variant chr15-90889880-A-G is described in ClinVar as Benign. ClinVar VariationId is 773300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002005.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FES	NM_002005.4	MANE Select	c.967A>G	p.Met323Val	missense	Exon 8 of 19	NP_001996.1	P07332-1
FES	NM_001143783.1		c.793A>G	p.Met265Val	missense	Exon 6 of 17	NP_001137255.1	P07332-3
FES	NM_001143784.1		c.967A>G	p.Met323Val	missense	Exon 7 of 17	NP_001137256.1	P07332-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FES	ENST00000328850.8	TSL:1 MANE Select	c.967A>G	p.Met323Val	missense	Exon 8 of 19	ENSP00000331504.3	P07332-1
FES	ENST00000394300.7	TSL:1	c.793A>G	p.Met265Val	missense	Exon 6 of 17	ENSP00000377837.3	P07332-3
FES	ENST00000444422.2	TSL:1	c.967A>G	p.Met323Val	missense	Exon 7 of 17	ENSP00000400868.2	P07332-4

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2168

AN:

151692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0471

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00938

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.0159

GnomAD2 exomes

AF:

0.00413

AC:

1038

AN:

251164

AF XY:

0.00334

show subpopulations

Gnomad AFR exome

AF:

0.0476

Gnomad AMR exome

AF:

0.00434

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000598

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00201

AC:

2933

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1342

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.0534

AC:

1789

AN:

33480

American (AMR)

AF:

0.00458

AC:

205

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000325

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53192

Middle Eastern (MID)

AF:

0.00936

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000489

AC:

544

AN:

1111992

Other (OTH)

AF:

0.00502

AC:

303

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

175

350

526

701

876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.0143

AC:

2177

AN:

151812

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1063

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.0472

AC:

1953

AN:

41360

American (AMR)

AF:

0.00937

AC:

143

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000618

AC:

AN:

67928

Other (OTH)

AF:

0.0157

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

107

214

320

427

534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00509

Hom.:

Bravo

AF:

0.0161

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0485

AC:

213

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00488

AC:

593

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000948

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.7

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.097

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

0.56

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.31

REVEL

Benign

0.10

Sift

Benign

0.28

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.081

MVP

0.49

MPC

0.33

ClinPred

0.0060

GERP RS

-4.0

Varity_R

0.076

gMVP

0.12

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over