NM_001367949.2:c.12938-6A>T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT3	NM_001367949.2	c.12938-6A>T		splice_region_variant, intron_variant	Intron 24 of 27	ENST00000525166.6	NP_001354878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT3	ENST00000525166.6	c.12938-6A>T		splice_region_variant, intron_variant	Intron 24 of 27	5	NM_001367949.2	ENSP00000432586.2

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

GnomAD3 exomes AF: 0.115 AC: 25159 AN: 218650 Hom.: 1618 AF XY: 0.114 AC XY: 13356 AN XY: 117422

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 SAS exome AF: 0.125

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

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.0984

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.104

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

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0936 Hom.: 239

Bravo AF: 0.0826

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs12421052; hg19: chr11-92620160;