Genetic Variant AP1G1:c.202-1039G>A (chr16-71775631-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128.6(AP1G1):c.202-1039G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,858 control chromosomes in the GnomAD database, including 9,668 homozygotes. 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: 𝑓 0.34 ( 9668 hom., cov: 31)

Consequence

AP1G1
NM_001128.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.476

Publications

2 publications found

Variant links:

Genes affected

AP1G1 (HGNC:555): (adaptor related protein complex 1 subunit gamma 1) Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. The adaptin family of proteins is composed of four classes of molecules named alpha, beta-, beta prime- and gamma- adaptins. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. The protein encoded by this gene is a gamma-adaptin protein and it belongs to the adaptor complexes large subunits family. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

AP1G1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: ClinGen
Usmani-Riazuddin syndrome, autosomal dominant
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Usmani-Riazuddin syndrome, autosomal recessive
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

AP1G1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1G1	NM_001128.6 link	c.202-1039G>A		intron_variant	Intron 2 of 22	ENST00000299980.9	NP_001119.3	O43747-1Q8IY97
AP1G1	NM_001030007.2 link	c.202-1039G>A		intron_variant	Intron 2 of 23		NP_001025178.1	O43747-2Q8IY97A0A140VJE7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1G1	ENST00000299980.9 link	c.202-1039G>A		intron_variant	Intron 2 of 22	1	NM_001128.6	ENSP00000299980.4		O43747-1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51870

AN:

151740

Hom.:

9664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.763

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.311

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

GnomAD4 genome

AF:

0.342

AC:

51884

AN:

151858

Hom.:

9668

Cov.:

AF XY:

0.347

AC XY:

25719

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.263

AC:

10878

AN:

41430

American (AMR)

AF:

0.447

AC:

6812

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1153

AN:

3468

East Asian (EAS)

AF:

0.762

AC:

3941

AN:

5170

South Asian (SAS)

AF:

0.334

AC:

1604

AN:

4804

European-Finnish (FIN)

AF:

0.365

AC:

3827

AN:

10482

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22604

AN:

67948

Other (OTH)

AF:

0.310

AC:

652

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1649

3297

4946

6594

8243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.333

Hom.:

1108

Bravo

AF:

0.350

Asia WGS

AF:

0.513

AC:

1781

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.0

(source)

DANN

Benign

0.70

PhyloP100

0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over