11-92352807-T-C

Variant names:

• chr11-92352807-T-C
• NM_001367949.2:c.695T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001367949.2(FAT3):​c.695T>C​(p.Leu232Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAT3 NM_001367949.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

Genes affected

FAT3 (HGNC:23112): (FAT atypical cadherin 3) Predicted to enable calcium ion binding activity. Predicted to be involved in cell-cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of dendrite development; neuron migration; and retina layer formation. Predicted to be located in dendrite and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT3	NM_001367949.2	c.695T>C	p.Leu232Ser	missense_variant	Exon 2 of 28	ENST00000525166.6	NP_001354878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT3	ENST00000525166.6	c.695T>C	p.Leu232Ser	missense_variant	Exon 2 of 28	5	NM_001367949.2	ENSP00000432586.2
FAT3	ENST00000409404.6	c.695T>C	p.Leu232Ser	missense_variant	Exon 1 of 25	5		ENSP00000387040.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.695T>C (p.L232S) alteration is located in exon 1 (coding exon 1) of the FAT3 gene. This alteration results from a T to C substitution at nucleotide position 695, causing the leucine (L) at amino acid position 232 to be replaced by a serine (S). 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D;D
Vest4		0.87
MutPred		0.44		Loss of stability (P = 0.0072);.;
MVP		0.65
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.59
gMVP		0.61

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: chr11-92085973;