Genetic Variant FRAT1:p.Pro60Leu (chr10-97319632-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005479.4(FRAT1):c.179C>T(p.Pro60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 150,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Failed GnomAD Quality Control

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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>T	p.Pro60Leu	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>T	p.Pro60Leu	missense	Exon 1 of 1	ENSP00000360060.3	Q92837

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000266

AC:

AN:

1127496

Hom.:

Cov.:

AF XY:

0.00000368

AC XY:

AN XY:

542940

show subpopulations

African (AFR)

AF:

0.0000834

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:

0.00

AC:

AN:

44960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.0000199

AC:

AN:

150744

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73592

show subpopulations

African (AFR)

AF:

0.0000727

AC:

AN:

41246

American (AMR)

AF:

0.00

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67614

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.87

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.5

PhyloP100

1.4

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.33

Sift

Uncertain

0.0070

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.083

MutPred

0.62

Loss of glycosylation at P60 (P = 0.0224)

MVP

0.25

MPC

2.4

ClinPred

0.97

GERP RS

3.0

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.28

gMVP

0.16

Mutation Taster

=68/32

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

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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