10-97319805-C-T

Variant names:

• chr10-97319805-C-T
• NM_005479.4:c.352C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005479.4(FRAT1):​c.352C>T​(p.Arg118Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,195,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: FRAT1 NM_005479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.137

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAT1	NM_005479.4	c.352C>T	p.Arg118Cys	missense_variant	Exon 1 of 1	ENST00000371021.5	NP_005470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAT1	ENST00000371021.5	c.352C>T	p.Arg118Cys	missense_variant	Exon 1 of 1	6	NM_005479.4	ENSP00000360060.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000753 AC: 9 AN: 1195200 Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 4 AN XY: 580386

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000907

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.352C>T (p.R118C) alteration is located in exon 1 (coding exon 1) of the FRAT1 gene. This alteration results from a C to T substitution at nucleotide position 352, causing the arginine (R) at amino acid position 118 to be replaced by a cysteine (C). 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	0.31
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.081
Sift	Benign	0.12	T
Sift4G	Uncertain	0.058	T
Polyphen		0.075	B
Vest4		0.17
MutPred		0.75		Loss of methylation at R118 (P = 0.0075);
MVP		0.31
MPC		1.6
ClinPred		0.11	T
GERP RS		1.1
Varity_R		0.11
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-99079562;