1-113901822-TGA-ACT

Variant names:

• chr1-113901822-TGA-ACT
• NM_001253852.3:c.400_402delTCAinsAGT
• AP4B1 p.135

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001253852.3(AP4B1):​c.400_402delTCAinsAGT​(p.135) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S134S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP4B1 NM_001253852.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.01
• Publications: 0 publications found

Genes affected

AP4B1 (HGNC:572): (adaptor related protein complex 4 subunit beta 1) This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AP4B1 Gene-Disease associations (from GenCC):

• AP-4 deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 47

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP4B1	NM_001253852.3	MANE Select	c.400_402delTCAinsAGT	p.135	synonymous	N/A	NP_001240781.1	Q9Y6B7-1
	AP4B1	NM_001438373.1		c.400_402delTCAinsAGT	p.135	synonymous	N/A	NP_001425302.1
	AP4B1	NM_006594.5		c.400_402delTCAinsAGT	p.135	synonymous	N/A	NP_006585.2	Q9Y6B7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP4B1	ENST00000369569.6	TSL:1 MANE Select	c.400_402delTCAinsAGT	p.135	synonymous	N/A	ENSP00000358582.1	Q9Y6B7-1
	AP4B1	ENST00000256658.8	TSL:1	c.400_402delTCAinsAGT	p.135	synonymous	N/A	ENSP00000256658.4	Q9Y6B7-1
	AP4B1	ENST00000863127.1		c.400_402delTCAinsAGT	p.135	synonymous	N/A	ENSP00000533186.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-114444444;