rs78040862

Variant names:

• chr4-125487377-T-A
• NM_001291303.3:c.12855T>A

Your query was ambiguous. Multiple possible variants found:

• chr4-125487377-T-A
• chr4-125487377-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001291303.3(FAT4):​c.12855T>A​(p.Asp4285Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,530 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D4285D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FAT4 NM_001291303.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

FAT4 (HGNC:23109): (FAT atypical cadherin 4) The protein encoded by this gene is a member of the protocadherin family. This gene may play a role in regulating planar cell polarity (PCP). Studies in mice suggest that loss of PCP signaling may cause cystic kidney disease, and mutations in this gene have been associated with Van Maldergem Syndrome 2. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT4	NM_001291303.3	c.12855T>A	p.Asp4285Glu	missense_variant	Exon 17 of 18	ENST00000394329.9	NP_001278232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT4	ENST00000394329.9	c.12855T>A	p.Asp4285Glu	missense_variant	Exon 17 of 18	5	NM_001291303.3	ENSP00000377862.4
FAT4	ENST00000335110.5	c.7572T>A	p.Asp2524Glu	missense_variant	Exon 14 of 15	1		ENSP00000335169.5
FAT4	ENST00000674496.2	c.7626T>A	p.Asp2542Glu	missense_variant	Exon 16 of 17			ENSP00000501473.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461530 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.050	N;N
REVEL	Uncertain	0.55
Sift	Benign	0.90	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.76
MutPred		0.82		Gain of glycosylation at Y4279 (P = 0.0635);.;
MVP		0.75
MPC		0.38
ClinPred		0.73	D
GERP RS		2.9
Varity_R		0.079
gMVP		0.65

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-126408532;