chr11-92352457-C-T

Variant names:

• chr11-92352457-C-T
• rs76685441
• NM_001367949.2:c.345C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001367949.2(FAT3):​c.345C>T​(p.Ala115Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,612,444 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (20 hom.)
• Consequence: FAT3 NM_001367949.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.560
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 11-92352457-C-T is Benign according to our data. Variant chr11-92352457-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2642266.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.56 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.345C>T	p.Ala115Ala	synonymous	Exon 2 of 28	NP_001354878.1	Q8TDW7-1
	FAT3	NM_001008781.3		c.345C>T	p.Ala115Ala	synonymous	Exon 2 of 26	NP_001008781.2	Q8TDW7-3
	FAT3	NM_001378141.1		c.345C>T	p.Ala115Ala	synonymous	Exon 2 of 4	NP_001365070.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT3	ENST00000525166.6	TSL:5 MANE Select	c.345C>T	p.Ala115Ala	synonymous	Exon 2 of 28	ENSP00000432586.2	Q8TDW7-1
	FAT3	ENST00000409404.6	TSL:5	c.345C>T	p.Ala115Ala	synonymous	Exon 1 of 25	ENSP00000387040.2	Q8TDW7-3

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 491 AN: 152082 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00773

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00445

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00278 AC: 692 AN: 248612 AF XY: 0.00276

Gnomad AFR exome AF: 0.000905

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00431

Gnomad OTH exome AF: 0.00515

GnomAD4 exome AF: 0.00431 AC: 6293 AN: 1460244 Hom.: 20 Cov.: 31 AF XY: 0.00412 AC XY: 2996 AN XY: 726424

African (AFR) AF: 0.00111 AC: 37 AN: 33442

American (AMR) AF: 0.00504 AC: 225 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 85416

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53362

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00513 AC: 5697 AN: 1111520

Other (OTH) AF: 0.00471 AC: 284 AN: 60328

GnomAD4 genome AF: 0.00323 AC: 491 AN: 152200 Hom.: 2 Cov.: 32 AF XY: 0.00318 AC XY: 237 AN XY: 74432

African (AFR) AF: 0.00106 AC: 44 AN: 41498

American (AMR) AF: 0.00772 AC: 118 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00446 AC: 303 AN: 68010

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00365 Hom.: 0

Bravo AF: 0.00400

EpiCase AF: 0.00338

EpiControl AF: 0.00528

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	FAT3-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		0.56
PromoterAI		-0.00040	Neutral
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76685441; hg19: chr11-92085623; COSMIC: COSV53183764; COSMIC: COSV53183764;