NM_001367949.2:c.4196-1363A>G

Variant names:

• chr11-92772678-A-G
• rs10765560
• NM_001367949.2:c.4196-1363A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001367949.2(FAT3):​c.4196-1363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,870 control chromosomes in the GnomAD database, including 16,388 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 0.45 (16388 hom., cov: 32)
• Consequence: FAT3 NM_001367949.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT3	NM_001367949.2	c.4196-1363A>G		intron_variant	Intron 6 of 27	ENST00000525166.6	NP_001354878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT3	ENST00000525166.6	c.4196-1363A>G		intron_variant	Intron 6 of 27	5	NM_001367949.2	ENSP00000432586.2
FAT3	ENST00000409404.6	c.4196-1363A>G		intron_variant	Intron 5 of 24	5		ENSP00000387040.2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68613 AN: 151752 Hom.: 16385 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.452 AC: 68652 AN: 151870 Hom.: 16388 Cov.: 32 AF XY: 0.457 AC XY: 33896 AN XY: 74208

African (AFR) AF: 0.302 AC: 12502 AN: 41458

American (AMR) AF: 0.508 AC: 7754 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1726 AN: 3466

East Asian (EAS) AF: 0.594 AC: 3066 AN: 5160

South Asian (SAS) AF: 0.640 AC: 3079 AN: 4812

European-Finnish (FIN) AF: 0.477 AC: 5022 AN: 10536

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33759 AN: 67874

Other (OTH) AF: 0.478 AC: 1004 AN: 2102

Alfa AF: 0.468 Hom.: 2104

Bravo AF: 0.446

Asia WGS AF: 0.546 AC: 1892 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		0.57
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: rs10765560; hg19: chr11-92505844;