rs536537428

Variant names:

• chr11-92352664-C-T
• rs536537428
• NM_001367949.2:c.552C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-92352664-C-T
• chr11-92352664-C-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001367949.2(FAT3):​c.552C>T​(p.Asp184Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,613,766 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (2 hom.)
• Consequence: FAT3 NM_001367949.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.111
• Publications: 1 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=-0.51).
• BP6: Variant 11-92352664-C-T is Benign according to our data. Variant chr11-92352664-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3039646.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.111 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 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.552C>T	p.Asp184Asp	synonymous	Exon 2 of 28	NP_001354878.1	Q8TDW7-1
	FAT3	NM_001008781.3		c.552C>T	p.Asp184Asp	synonymous	Exon 2 of 26	NP_001008781.2	Q8TDW7-3
	FAT3	NM_001378141.1		c.552C>T	p.Asp184Asp	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.552C>T	p.Asp184Asp	synonymous	Exon 2 of 28	ENSP00000432586.2	Q8TDW7-1
	FAT3	ENST00000409404.6	TSL:5	c.552C>T	p.Asp184Asp	synonymous	Exon 1 of 25	ENSP00000387040.2	Q8TDW7-3

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000326 AC: 81 AN: 248468 AF XY: 0.000430

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00111

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.0000622

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000138 AC: 201 AN: 1461508 Hom.: 2 Cov.: 32 AF XY: 0.000175 AC XY: 127 AN XY: 727018

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39694

South Asian (SAS) AF: 0.00147 AC: 127 AN: 86250

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53358

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111818

Other (OTH) AF: 0.000215 AC: 13 AN: 60370

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74436

African (AFR) AF: 0.0000722 AC: 3 AN: 41560

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5168

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000125

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FAT3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.16
DANN	Benign	0.65
PhyloP100		0.11
Mutation Taster		=83/17	polymorphism

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: rs536537428; hg19: chr11-92085830; COSMIC: COSV53160911; COSMIC: COSV53160911;