11-92886994-A-T

Variant names:

• chr11-92886994-A-T
• rs12421052
• NM_001367949.2:c.12938-6A>T

Variant summary

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

The NM_001367949.2(FAT3):​c.12938-6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,593,294 control chromosomes in the GnomAD database, including 9,212 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.086 (720 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8492 hom.)
• Consequence: FAT3 NM_001367949.2 splice_region, intron
• Scores: Splicing: ADA: 0.00005853
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367949.2. 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
	FAT3	NM_001367949.2	MANE Select	c.12938-6A>T		splice_region intron	N/A	NP_001354878.1	Q8TDW7-1
	FAT3	NM_001008781.3		c.12938-6A>T		splice_region intron	N/A	NP_001008781.2	Q8TDW7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT3	ENST00000525166.6	TSL:5 MANE Select	c.12938-6A>T		splice_region intron	N/A	ENSP00000432586.2	Q8TDW7-1
	FAT3	ENST00000409404.6	TSL:5	c.12938-6A>T		splice_region intron	N/A	ENSP00000387040.2	Q8TDW7-3
	FAT3	ENST00000469900.1	TSL:3	n.130A>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13031 AN: 152168 Hom.: 716 Cov.: 33

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0775

GnomAD2 exomes AF: 0.115 AC: 25159 AN: 218650 AF XY: 0.114

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.141

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.0995

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.106 AC: 152415 AN: 1441008 Hom.: 8492 Cov.: 30 AF XY: 0.106 AC XY: 75683 AN XY: 714534

African (AFR) AF: 0.0176 AC: 586 AN: 33248

American (AMR) AF: 0.160 AC: 6576 AN: 41208

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 2527 AN: 25684

East Asian (EAS) AF: 0.128 AC: 5031 AN: 39242

South Asian (SAS) AF: 0.124 AC: 10216 AN: 82440

European-Finnish (FIN) AF: 0.151 AC: 7913 AN: 52402

Middle Eastern (MID) AF: 0.0976 AC: 561 AN: 5750

European-Non Finnish (NFE) AF: 0.102 AC: 112816 AN: 1101264

Other (OTH) AF: 0.104 AC: 6189 AN: 59770

GnomAD4 genome AF: 0.0856 AC: 13040 AN: 152286 Hom.: 720 Cov.: 33 AF XY: 0.0901 AC XY: 6705 AN XY: 74438

African (AFR) AF: 0.0208 AC: 865 AN: 41570

American (AMR) AF: 0.128 AC: 1954 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3472

East Asian (EAS) AF: 0.137 AC: 710 AN: 5178

South Asian (SAS) AF: 0.120 AC: 578 AN: 4826

European-Finnish (FIN) AF: 0.148 AC: 1567 AN: 10612

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6834 AN: 68014

Other (OTH) AF: 0.0762 AC: 161 AN: 2112

Alfa AF: 0.0936 Hom.: 239

Bravo AF: 0.0826

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.52
PhyloP100		-0.13
Mutation Taster		=15/85	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000059
dbscSNV1_RF	Benign	0.030
SpliceAI score (max)		0.080		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: rs12421052; hg19: chr11-92620160; COSMIC: COSV107310902;