NM_001128126.3:c.-77G>A

Variant names:

• chr14-31025782-G-A
• rs78648016
• NM_001128126.3:c.-77G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.150
• Publications: 3 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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128126.3. 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
	AP4S1	NM_001128126.3	MANE Select	c.-77G>A		5_prime_UTR	Exon 1 of 6	NP_001121598.1	Q9Y587-1
	STRN3	NM_001083893.2	MANE Select	c.282+122C>T		intron	N/A	NP_001077362.1	Q13033-1
	AP4S1	NM_007077.5		c.-77G>A		5_prime_UTR	Exon 1 of 6	NP_009008.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP4S1	ENST00000542754.7	TSL:1 MANE Select	c.-77G>A		5_prime_UTR	Exon 1 of 6	ENSP00000438170.2	Q9Y587-1
	AP4S1	ENST00000334725.8	TSL:1	c.-77G>A		5_prime_UTR	Exon 1 of 7	ENSP00000334484.4	Q9Y587-4
	STRN3	ENST00000357479.10	TSL:5 MANE Select	c.282+122C>T		intron	N/A	ENSP00000350071.5	Q13033-1

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7952 AN: 152170 Hom.: 343 Cov.: 31

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.: 17 AF XY: 0.0461 AC XY: 27669 AN XY: 600732

African (AFR) AF: 0.0427 AC: 1189 AN: 27846

American (AMR) AF: 0.135 AC: 4277 AN: 31632

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 1393 AN: 20838

East Asian (EAS) AF: 0.211 AC: 7227 AN: 34226

South Asian (SAS) AF: 0.0712 AC: 4830 AN: 67836

European-Finnish (FIN) AF: 0.0451 AC: 1470 AN: 32574

Middle Eastern (MID) AF: 0.0295 AC: 109 AN: 3690

European-Non Finnish (NFE) AF: 0.0343 AC: 32361 AN: 943168

Other (OTH) AF: 0.0536 AC: 2782 AN: 51862

GnomAD4 genome AF: 0.0524 AC: 7974 AN: 152288 Hom.: 351 Cov.: 31 AF XY: 0.0549 AC XY: 4085 AN XY: 74464

African (AFR) AF: 0.0437 AC: 1817 AN: 41570

American (AMR) AF: 0.102 AC: 1562 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 224 AN: 3472

East Asian (EAS) AF: 0.213 AC: 1097 AN: 5162

South Asian (SAS) AF: 0.0702 AC: 339 AN: 4828

European-Finnish (FIN) AF: 0.0533 AC: 566 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0322 AC: 2189 AN: 68024

Other (OTH) AF: 0.0543 AC: 115 AN: 2116

Alfa AF: 0.0427 Hom.: 366

Bravo AF: 0.0577

Asia WGS AF: 0.154 AC: 532 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.2
DANN	Benign	0.92
PhyloP100		0.15
PromoterAI		0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78648016; hg19: chr14-31494988;