rs1060503026

Variant names:

• chr15-50950099-A-G
• rs1060503026
• NM_007347.5:c.1478A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-50950099-A-G
• chr15-50950099-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007347.5(AP4E1):​c.1478A>G​(p.Gln493Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: AP4E1 NM_007347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70

Genes affected

AP4E1 (HGNC:573): (adaptor related protein complex 4 subunit epsilon 1) This gene encodes a member of the adaptor complexes large subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is a large subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Disruption of this gene may be associated with cerebral palsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16873336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP4E1	NM_007347.5	c.1478A>G	p.Gln493Arg	missense_variant	Exon 13 of 21	ENST00000261842.10	NP_031373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP4E1	ENST00000261842.10	c.1478A>G	p.Gln493Arg	missense_variant	Exon 13 of 21	1	NM_007347.5	ENSP00000261842.5
AP4E1	ENST00000560508.1	c.1253A>G	p.Gln418Arg	missense_variant	Exon 13 of 21	1		ENSP00000452976.1
AP4E1	ENST00000558439.5	n.*602A>G		non_coding_transcript_exon_variant	Exon 13 of 21	1		ENSP00000452712.1
AP4E1	ENST00000561393.5	n.*522A>G		non_coding_transcript_exon_variant	Exon 12 of 20	1		ENSP00000452711.1
AP4E1	ENST00000558439.5	n.*602A>G		3_prime_UTR_variant	Exon 13 of 21	1		ENSP00000452712.1
AP4E1	ENST00000561393.5	n.*522A>G		3_prime_UTR_variant	Exon 12 of 20	1		ENSP00000452711.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000936 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.046
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.067
Sift	Benign	0.20	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.56		Gain of catalytic residue at S494 (P = 0.1208);.;
MVP		0.35
MPC		0.12
ClinPred		0.63	D
GERP RS		5.0
Varity_R		0.22
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs1060503026; hg19: chr15-51242296;