Variant chr15-90885222-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002005.4(FES):c.177G>C(p.Gln59His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FES
NM_002005.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

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:

FES (HGNC:):

FES links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25575313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FES	NM_002005.4 linkuse as main transcript	c.177G>C	p.Gln59His	missense_variant	2/19	ENST00000328850.8	NP_001996.1	P07332-1A0A024RC92

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FES	ENST00000328850.8 linkuse as main transcript	c.177G>C	p.Gln59His	missense_variant	2/19	1	NM_002005.4	ENSP00000331504.3		P07332-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249994

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726820

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.177G>C (p.Q59H) alteration is located in exon 2 (coding exon 1) of the FES gene. This alteration results from a G to C substitution at nucleotide position 177, causing the glutamine (Q) at amino acid position 59 to be replaced by a histidine (H). 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

0.098

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.16

T;.;T;T;T;.;.;.

Eigen

Benign

-0.096

Eigen_PC

Benign

-0.095

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

T;D;T;D;T;T;D;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;.;.;.;.;L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N;N

REVEL

Benign

0.060

Sift

Benign

0.14

T;D;T;D;T;T;D;T

Sift4G

Benign

0.16

T;T;T;T;T;T;T;T

Polyphen

0.0040

B;D;.;D;.;.;B;D

Vest4

0.17

MutPred

0.56

Gain of catalytic residue at Q59 (P = 0.1276);Gain of catalytic residue at Q59 (P = 0.1276);Gain of catalytic residue at Q59 (P = 0.1276);Gain of catalytic residue at Q59 (P = 0.1276);Gain of catalytic residue at Q59 (P = 0.1276);Gain of catalytic residue at Q59 (P = 0.1276);Gain of catalytic residue at Q59 (P = 0.1276);Gain of catalytic residue at Q59 (P = 0.1276);

MVP

0.72

MPC

0.31

ClinPred

0.21

GERP RS

3.4

Varity_R

0.089

gMVP

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over