10-97319481-G-A

Variant names:

• chr10-97319481-G-A
• NM_005479.4:c.28G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_005479.4(FRAT1):​c.28G>A​(p.Glu10Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,315,360 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: FRAT1 NM_005479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25556475).
• BS2: High AC in GnomAdExome4 at 5 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.28G>A	p.Glu10Lys	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.28G>A	p.Glu10Lys	missense	Exon 1 of 1	ENSP00000360060.3	Q92837

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000380 AC: 5 AN: 1315360 Hom.: 0 Cov.: 31 AF XY: 0.00000462 AC XY: 3 AN XY: 648978

African (AFR) AF: 0.00 AC: 0 AN: 26910

American (AMR) AF: 0.00 AC: 0 AN: 28234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23104

East Asian (EAS) AF: 0.00 AC: 0 AN: 28270

South Asian (SAS) AF: 0.0000138 AC: 1 AN: 72666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5186

European-Non Finnish (NFE) AF: 0.00000383 AC: 4 AN: 1043868

Other (OTH) AF: 0.00 AC: 0 AN: 54394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.00037	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.039
Sift	Benign	0.21	T
Sift4G	Uncertain	0.046	D
Polyphen		0.042	B
Vest4		0.21
MutPred		0.56		Gain of ubiquitination at E10 (P = 0.0069)
MVP		0.61
MPC		2.3
ClinPred		0.81	D
GERP RS		1.9
PromoterAI		-0.43	Neutral
Varity_R		0.19
gMVP		0.11
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

hg19: chr10-99079238;