Variant 14-31025782-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001128126.3(AP4S1):c.-77G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,365,960 control chromosomes in the GnomAD database, including 2,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 351 hom., cov: 31)

Exomes 𝑓: 0.046 ( 2121 hom. )

Consequence

AP4S1
NM_001128126.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.150

Variant links:

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 links:

STRN3 (HGNC:15720): (striatin 3) Enables armadillo repeat domain binding activity; protein phosphatase 2A binding activity; and small GTPase binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; nucleoplasm; and plasma membrane. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

STRN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 14-31025782-G-A is Benign according to our data. Variant chr14-31025782-G-A is described in ClinVar as [Benign]. Clinvar id is 380897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP4S1	NM_001128126.3 linkuse as main transcript	c.-77G>A		5_prime_UTR_variant	1/6	ENST00000542754.7	NP_001121598.1	Q9Y587-1
STRN3	NM_001083893.2 linkuse as main transcript	c.282+122C>T		intron_variant		ENST00000357479.10	NP_001077362.1	Q13033-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP4S1	ENST00000542754 linkuse as main transcript	c.-77G>A		5_prime_UTR_variant	1/6	1	NM_001128126.3	ENSP00000438170.2		Q9Y587-1
STRN3	ENST00000357479.10 linkuse as main transcript	c.282+122C>T		intron_variant		5	NM_001083893.2	ENSP00000350071.5		Q13033-1

Frequencies

GnomAD3 genomes

AF:

0.0523

AC:

7952

AN:

152170

Hom.:

343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0438

Gnomad AMI

AF:

0.0626

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0645

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.0700

Gnomad FIN

AF:

0.0533

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0322

Gnomad OTH

AF:

0.0478

GnomAD4 exome

AF:

0.0458

AC:

55638

AN:

1213672

Hom.:

2121

Cov.:

AF XY:

0.0461

AC XY:

27669

AN XY:

600732

show subpopulations

Gnomad4 AFR exome

AF:

0.0427

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.0668

Gnomad4 EAS exome

AF:

0.211

Gnomad4 SAS exome

AF:

0.0712

Gnomad4 FIN exome

AF:

0.0451

Gnomad4 NFE exome

AF:

0.0343

Gnomad4 OTH exome

AF:

0.0536

GnomAD4 genome

AF:

0.0524

AC:

7974

AN:

152288

Hom.:

351

Cov.:

AF XY:

0.0549

AC XY:

4085

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0437

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.0645

Gnomad4 EAS

AF:

0.213

Gnomad4 SAS

AF:

0.0702

Gnomad4 FIN

AF:

0.0533

Gnomad4 NFE

AF:

0.0322

Gnomad4 OTH

AF:

0.0543

Alfa

AF:

0.0428

Hom.:

Bravo

AF:

0.0577

Asia WGS

AF:

0.154

AC:

532

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 15, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.2

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over