rs1555461061

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_007347.5(AP4E1):​c.2019A>C​(p.Gly673Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Consequence

AP4E1
NM_007347.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.768
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 15-50984074-A-C is Benign according to our data. Variant chr15-50984074-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 458248.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.768 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AP4E1NM_007347.5 linkc.2019A>C p.Gly673Gly synonymous_variant 16/21 ENST00000261842.10 NP_031373.2 Q9UPM8-1B4DM48

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AP4E1ENST00000261842.10 linkc.2019A>C p.Gly673Gly synonymous_variant 16/211 NM_007347.5 ENSP00000261842.5 Q9UPM8-1
AP4E1ENST00000560508.1 linkc.1794A>C p.Gly598Gly synonymous_variant 16/211 ENSP00000452976.1 Q9UPM8-2
AP4E1ENST00000558439.5 linkn.*1143A>C non_coding_transcript_exon_variant 16/211 ENSP00000452712.1 H0YK95
AP4E1ENST00000561393.5 linkn.*1063A>C non_coding_transcript_exon_variant 15/201 ENSP00000452711.1 H0YK94
AP4E1ENST00000558439.5 linkn.*1143A>C 3_prime_UTR_variant 16/211 ENSP00000452712.1 H0YK95
AP4E1ENST00000561393.5 linkn.*1063A>C 3_prime_UTR_variant 15/201 ENSP00000452711.1 H0YK94

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 03, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
11
DANN
Benign
0.73

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555461061; hg19: chr15-51276271; API