15-50950080-T-G

Variant names:

• chr15-50950080-T-G
• NM_007347.5:c.1459T>G

Variant summary

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

The NM_007347.5(AP4E1):​c.1459T>G​(p.Leu487Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AP4E1 NM_007347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483

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 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
AP4E1	NM_007347.5	c.1459T>G	p.Leu487Val	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.1459T>G	p.Leu487Val	missense_variant	Exon 13 of 21	1	NM_007347.5	ENSP00000261842.5
AP4E1	ENST00000560508.1	c.1234T>G	p.Leu412Val	missense_variant	Exon 13 of 21	1		ENSP00000452976.1
AP4E1	ENST00000558439.5	n.*583T>G		non_coding_transcript_exon_variant	Exon 13 of 21	1		ENSP00000452712.1
AP4E1	ENST00000561393.5	n.*503T>G		non_coding_transcript_exon_variant	Exon 12 of 20	1		ENSP00000452711.1
AP4E1	ENST00000558439.5	n.*583T>G		3_prime_UTR_variant	Exon 13 of 21	1		ENSP00000452712.1
AP4E1	ENST00000561393.5	n.*503T>G		3_prime_UTR_variant	Exon 12 of 20	1		ENSP00000452711.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460796 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726772

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: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	0.078
Eigen_PC	Benign	-0.076
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;.
Vest4		0.46
MutPred		0.56		Gain of helix (P = 0.132);.;
MVP		0.22
MPC		0.51
ClinPred		0.98	D
GERP RS		-2.4
Varity_R		0.58
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.37		Position offset: -1

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: chr15-51242277;