dbSNP rs772795359: FER:p.Met102Thr (chr5-108832867-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005246.4(FER):c.305T>C(p.Met102Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,608,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

FER
NM_005246.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Publications

0 publications found

Variant links:

Genes affected

FER (HGNC:3655): (FER tyrosine kinase) The protein encoded by this gene is a member of the FPS/FES family of non-transmembrane receptor tyrosine kinases. It regulates cell-cell adhesion and mediates signaling from the cell surface to the cytoskeleton via growth factor receptors. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome X. [provided by RefSeq, Apr 2015]

FER links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.078492135).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FER	NM_005246.4	MANE Select	c.305T>C	p.Met102Thr	missense	Exon 4 of 20	NP_005237.2	P16591-1
FER	NM_001308038.2		c.305T>C	p.Met102Thr	missense	Exon 5 of 8	NP_001294967.1
FER	NM_001308028.2		c.-45+34478T>C		intron	N/A	NP_001294957.1	P16591-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FER	ENST00000281092.9	TSL:1 MANE Select	c.305T>C	p.Met102Thr	missense	Exon 4 of 20	ENSP00000281092.4	P16591-1
FER	ENST00000502752.1	TSL:1	n.630T>C		non_coding_transcript_exon	Exon 5 of 8
FER	ENST00000880768.1		c.305T>C	p.Met102Thr	missense	Exon 4 of 20	ENSP00000550827.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151838

Hom.:

Cov.:

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248440

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1457012

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

724838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33338

American (AMR)

AF:

0.00

AC:

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.00

AC:

AN:

39446

South Asian (SAS)

AF:

0.00

AC:

AN:

85584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1109004

Other (OTH)

AF:

0.0000333

AC:

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000659

AC:

AN:

151838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41316

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.080

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.0084

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.75

M_CAP

Benign

0.0051

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

3.5

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.14

REVEL

Benign

0.048

Sift

Benign

0.68

Sift4G

Benign

0.77

Polyphen

0.0

Vest4

0.36

MutPred

0.28

Loss of stability (P = 0.048)

MVP

0.25

MPC

0.20

ClinPred

0.25

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.11

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over