Variant 10-97319519-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005479.4(FRAT1):c.66G>C(p.Glu22Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,478,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

FRAT1
NM_005479.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.473

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006722212).

BS2

High AC in GnomAd4 at 161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAT1	NM_005479.4 linkuse as main transcript	c.66G>C	p.Glu22Asp	missense_variant	1/1	ENST00000371021.5	NP_005470.2	Q92837

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRAT1	ENST00000371021.5 linkuse as main transcript	c.66G>C	p.Glu22Asp	missense_variant	1/1	6	NM_005479.4	ENSP00000360060.3		Q92837

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000589

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000120

AC:

AN:

91424

Hom.:

AF XY:

0.0000394

AC XY:

AN XY:

50748

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.0000540

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000392

Gnomad NFE exome

AF:

0.0000302

Gnomad OTH exome

AF:

0.000367

GnomAD4 exome

AF:

0.000124

AC:

164

AN:

1326816

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

654632

show subpopulations

Gnomad4 AFR exome

AF:

0.00286

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.0000426

Gnomad4 EAS exome

AF:

0.0000689

Gnomad4 SAS exome

AF:

0.0000541

Gnomad4 FIN exome

AF:

0.000303

Gnomad4 NFE exome

AF:

0.0000457

Gnomad4 OTH exome

AF:

0.000290

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152024

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00369

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000230

Hom.:

Bravo

AF:

0.000982

ESP6500AA

AF:

0.00127

AC:

ESP6500EA

AF:

0.000131

AC:

ExAC

AF:

0.000184

AC:

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

Sep 01, 2021

The c.66G>C (p.E22D) alteration is located in exon 1 (coding exon 1) of the FRAT1 gene. This alteration results from a G to C substitution at nucleotide position 66, causing the glutamic acid (E) at amino acid position 22 to be replaced by an aspartic acid (D). 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

0.090

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.29

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.33

M_CAP

Benign

0.049

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.63

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.14

REVEL

Benign

0.030

Sift

Benign

0.61

Sift4G

Benign

0.18

Polyphen

0.017

Vest4

0.12

MutPred

0.36

Loss of helix (P = 0.0237);

MVP

0.34

MPC

1.0

ClinPred

0.013

GERP RS

0.79

Varity_R

0.060

gMVP

0.024

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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