Genetic Variant NM_005479.4:c.179C>A (chr10-97319632-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_005479.4(FRAT1):c.179C>A(p.Pro60Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000469 in 1,278,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P60R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

FRAT1
NM_005479.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

0 publications found

Variant links:

Genes affected

FRAT1 (HGNC:3944): (FRAT regulator of WNT signaling pathway 1) The protein encoded by this gene belongs to the GSK-3-binding protein family. The protein inhibits GSK-3-mediated phosphorylation of beta-catenin and positively regulates the Wnt signaling pathway. It may function in tumor progression and in lymphomagenesis. [provided by RefSeq, Oct 2008]

FRAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36244315).

BS2

High AC in GnomAd4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005479.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAT1	NM_005479.4	MANE Select	c.179C>A	p.Pro60Gln	missense	Exon 1 of 1	NP_005470.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAT1	ENST00000371021.5	TSL:6 MANE Select	c.179C>A	p.Pro60Gln	missense	Exon 1 of 1	ENSP00000360060.3	Q92837

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

150744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000509

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

35170

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000337

AC:

AN:

1127496

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

542940

show subpopulations

African (AFR)

AF:

0.00138

AC:

AN:

23978

American (AMR)

AF:

0.00

AC:

AN:

13656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16910

East Asian (EAS)

AF:

0.00

AC:

AN:

26030

South Asian (SAS)

AF:

0.0000305

AC:

AN:

32766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3136

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

942462

Other (OTH)

AF:

0.0000890

AC:

AN:

44960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.000146

AC:

AN:

150850

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73708

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

41362

American (AMR)

AF:

0.0000660

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67604

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.0000623

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.36

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.8

PhyloP100

1.4

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.23

Sift

Uncertain

0.0050

Sift4G

Benign

0.089

Polyphen

1.0

Vest4

0.083

MutPred

0.61

Loss of glycosylation at P60 (P = 0.0224)

MVP

0.23

MPC

2.3

ClinPred

0.93

GERP RS

3.0

PromoterAI

0.15

Neutral

(source)

Varity_R

0.37

gMVP

0.18

Mutation Taster

=95/5

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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