dbSNP rs1053978668: FRAT1:p.Pro108Ala (chr10-97319775-C-G) – 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_005479.4(FRAT1):c.322C>G(p.Pro108Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,273,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

FRAT1
NM_005479.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.287

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15916455).

BS2

High AC in GnomAd4 at 36 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.322C>G	p.Pro108Ala	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.322C>G	p.Pro108Ala	missense	Exon 1 of 1	ENSP00000360060.3	Q92837

Frequencies

GnomAD3 genomes

AF:

0.000238

AC:

AN:

151236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.000428

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

444

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR 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:

0.000392

AC:

440

AN:

1122538

Hom.:

Cov.:

AF XY:

0.000410

AC XY:

220

AN XY:

536684

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22548

American (AMR)

AF:

0.000125

AC:

AN:

8016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14504

East Asian (EAS)

AF:

0.00

AC:

AN:

25384

South Asian (SAS)

AF:

0.00

AC:

AN:

31028

European-Finnish (FIN)

AF:

0.0000411

AC:

AN:

24328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3034

European-Non Finnish (NFE)

AF:

0.000459

AC:

435

AN:

948460

Other (OTH)

AF:

0.0000663

AC:

AN:

45236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000238

AC:

AN:

151236

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73848

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41322

American (AMR)

AF:

0.00

AC:

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000428

AC:

AN:

67770

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000253

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

0.063

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.2

PhyloP100

0.29

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-2.1

REVEL

Benign

0.073

Sift

Benign

0.088

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.20

MutPred

0.32

Loss of glycosylation at P108 (P = 0.0561)

MVP

0.10

MPC

1.5

ClinPred

0.28

GERP RS

3.1

Varity_R

0.039

gMVP

0.062

Mutation Taster

=88/12

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