chr10-97319847-G-C

Position:

• chr10-97319847-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005479.4(FRAT1):​c.394G>C​(p.Glu132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,335,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: FRAT1 NM_005479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40899044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAT1	NM_005479.4	c.394G>C	p.Glu132Gln	missense_variant	1/1	ENST00000371021.5	NP_005470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRAT1	ENST00000371021.5	c.394G>C	p.Glu132Gln	missense_variant	1/1	6	NM_005479.4	ENSP00000360060.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000225 AC: 3 AN: 1335380 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 658272

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000707

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

The c.394G>C (p.E132Q) 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 394, causing the glutamic acid (E) at amino acid position 132 to be replaced by a glutamine (Q). 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	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.012
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.014	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.071
MutPred		0.73		Gain of MoRF binding (P = 0.0388);
MVP		0.27
MPC		1.9
ClinPred		0.77	D
GERP RS		2.3
Varity_R		0.17
gMVP		0.15

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

Other links and lift over

dbSNP: rs1296160877; hg19: chr10-99079604;