rs586699

Variant names:

• chr11-92556568-G-A
• rs586699
• NM_001367949.2:c.3607+31620G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367949.2(FAT3):​c.3607+31620G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,010 control chromosomes in the GnomAD database, including 23,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23002 hom., cov: 32)
• Consequence: FAT3 NM_001367949.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT3	NM_001367949.2	c.3607+31620G>A		intron_variant	Intron 3 of 27	ENST00000525166.6	NP_001354878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT3	ENST00000525166.6	c.3607+31620G>A		intron_variant	Intron 3 of 27	5	NM_001367949.2	ENSP00000432586.2
FAT3	ENST00000409404.6	c.3607+31620G>A		intron_variant	Intron 2 of 24	5		ENSP00000387040.2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82359 AN: 151892 Hom.: 22978 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.542 AC: 82422 AN: 152010 Hom.: 23002 Cov.: 32 AF XY: 0.552 AC XY: 40971 AN XY: 74280

African (AFR) AF: 0.440 AC: 18224 AN: 41438

American (AMR) AF: 0.638 AC: 9752 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1963 AN: 3462

East Asian (EAS) AF: 0.783 AC: 4044 AN: 5166

South Asian (SAS) AF: 0.740 AC: 3569 AN: 4824

European-Finnish (FIN) AF: 0.569 AC: 5995 AN: 10544

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36987 AN: 67974

Other (OTH) AF: 0.569 AC: 1200 AN: 2110

Alfa AF: 0.549 Hom.: 62854

Bravo AF: 0.542

Asia WGS AF: 0.726 AC: 2525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.096
DANN	Benign	0.55
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs586699; hg19: chr11-92289734;