ENST00000334725.8:c.*137C>G

Variant names:

• chr14-31084867-C-G
• rs143795469
• ENST00000334725.8:c.*137C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000334725.8(AP4S1):​c.*137C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 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: 6.8e-7 (0 hom.)
• Consequence: AP4S1 ENST00000334725.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586
• Publications: 0 publications found

Genes affected

AP4S1 (HGNC:575): (adaptor related protein complex 4 subunit sigma 1) This gene encodes a member of the adaptor complexes small 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 the small subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Mutations in this gene are associated with spastic quadriplegic cerebral palsy-6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Dec 2011]

AP4S1 Gene-Disease associations (from GenCC):

• AP-4 deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 52

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• AP4-related intellectual disability and spastic paraplegia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334725.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP4S1	NM_001128126.3	MANE Select	c.306+4283C>G		intron	N/A	NP_001121598.1
	AP4S1	NM_007077.5		c.465C>G	p.Thr155Thr	synonymous	Exon 6 of 6	NP_009008.2
	AP4S1	NM_001254726.2		c.393C>G	p.Thr131Thr	synonymous	Exon 5 of 5	NP_001241655.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP4S1	ENST00000334725.8	TSL:1	c.*137C>G		3_prime_UTR	Exon 7 of 7	ENSP00000334484.4
	AP4S1	ENST00000216366.9	TSL:1	c.*111C>G		3_prime_UTR	Exon 5 of 5	ENSP00000216366.5
	AP4S1	ENST00000542754.7	TSL:1 MANE Select	c.306+4283C>G		intron	N/A	ENSP00000438170.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.30
PhyloP100		-0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143795469; hg19: chr14-31554073;