rs144189610

Variant names:

• chr15-50997474-C-A
• NM_007347.5:c.2495C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-50997474-C-A
• chr15-50997474-C-G
• chr15-50997474-C-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_007347.5(AP4E1):​c.2495C>A​(p.Ser832*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AP4E1 NM_007347.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• 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.2495C>A	p.Ser832*	stop_gained	Exon 18 of 21	ENST00000261842.10	NP_031373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP4E1	ENST00000261842.10	c.2495C>A	p.Ser832*	stop_gained	Exon 18 of 21	1	NM_007347.5	ENSP00000261842.5
AP4E1	ENST00000560508.1	c.2270C>A	p.Ser757*	stop_gained	Exon 18 of 21	1		ENSP00000452976.1
AP4E1	ENST00000558439.5	n.*1619C>A		non_coding_transcript_exon_variant	Exon 18 of 21	1		ENSP00000452712.1
AP4E1	ENST00000561393.5	n.*1539C>A		non_coding_transcript_exon_variant	Exon 17 of 20	1		ENSP00000452711.1
AP4E1	ENST00000558439.5	n.*1619C>A		3_prime_UTR_variant	Exon 18 of 21	1		ENSP00000452712.1
AP4E1	ENST00000561393.5	n.*1539C>A		3_prime_UTR_variant	Exon 17 of 20	1		ENSP00000452711.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727152

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: 8.99e-7

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
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	34
DANN	Benign	0.96
Eigen	Benign	0.14
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.19	N
Vest4		0.26
GERP RS		3.0

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: chr15-51289671;