Variant 10-97319775-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 12/20 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

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 Likely_benign. Variant got -6 ACMG points.

BP4

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

BS2

High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAT1	NM_005479.4 linkuse as main transcript	c.322C>G	p.Pro108Ala	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.322C>G	p.Pro108Ala	missense_variant	1/1	6	NM_005479.4	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

GnomAD4 exome

AF:

0.000392

AC:

440

AN:

1122538

Hom.:

Cov.:

AF XY:

0.000410

AC XY:

220

AN XY:

536684

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000411

Gnomad4 NFE exome

AF:

0.000459

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000238

AC:

AN:

151236

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73848

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000428

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000253

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 26, 2024

The c.322C>G (p.P108A) alteration is located in exon 1 (coding exon 1) of the FRAT1 gene. This alteration results from a C to G substitution at nucleotide position 322, causing the proline (P) at amino acid position 108 to be replaced by an alanine (A). 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

0.063

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.38

CADD

Benign

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

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

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

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