1-113895154-T-G

Variant summary

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

The NM_001253852.3(AP4B1):c.2131A>C(p.Lys711Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AP4B1 NM_001253852.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

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-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

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/exons	MANE	UniProt
AP4B1	NM_001253852.3	c.2131A>C	p.Lys711Gln	missense_variant	10/10	ENST00000369569.6
AP4B1-AS1	NR_125965.1	n.415-2714T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP4B1	ENST00000369569.6	c.2131A>C	p.Lys711Gln	missense_variant	10/10	1	NM_001253852.3	P1
AP4B1-AS1	ENST00000419536.1	n.247-2714T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 47 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Jan 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Uncertain	-0.26	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		0.97	D;D;D
Vest4		0.35
MutPred		0.68		.;Loss of ubiquitination at K711 (P = 0.0063);Loss of ubiquitination at K711 (P = 0.0063);
MVP		0.87
MPC		0.59
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.67
gMVP		0.93

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-114437776;