14-23564163-G-C

Variant names:

• chr14-23564163-G-C
• rs10152092
• NM_003917.5:c.978-4C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003917.5(AP1G2):​c.978-4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00344 in 1,613,738 control chromosomes in the GnomAD database, including 163 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (84 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (79 hom.)
• Consequence: AP1G2 NM_003917.5 splice_region, intron
• Scores: Splicing: ADA: 0.04044
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 1 publications found

Genes affected

AP1G2 (HGNC:556): (adaptor related protein complex 1 subunit gamma 2) 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. This protein along with the complex is thought to function at some trafficking step in the complex pathways between the trans-Golgi network and the cell surface. [provided by RefSeq, Aug 2017]

AP1G2-AS1 (HGNC:55442): (AP1G2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003917.5. 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
	AP1G2	NM_003917.5	MANE Select	c.978-4C>G		splice_region intron	N/A	NP_003908.1	O75843
	AP1G2	NM_001282474.2		c.-170C>G		5_prime_UTR	Exon 9 of 20	NP_001269403.1	Q86U03
	AP1G2	NM_001354674.2		c.-170C>G		5_prime_UTR	Exon 10 of 21	NP_001341603.1	Q86U03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1G2	ENST00000397120.8	TSL:1 MANE Select	c.978-4C>G		splice_region intron	N/A	ENSP00000380309.3	O75843
	AP1G2	ENST00000308724.9	TSL:1	c.978-4C>G		splice_region intron	N/A	ENSP00000312442.5	O75843
	AP1G2	ENST00000460049.6	TSL:1	n.1147C>G		non_coding_transcript_exon	Exon 9 of 20

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2865 AN: 152164 Hom.: 85 Cov.: 33

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.00494 AC: 1234 AN: 249776 AF XY: 0.00348

Gnomad AFR exome AF: 0.0652

Gnomad AMR exome AF: 0.00450

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00184 AC: 2687 AN: 1461456 Hom.: 79 Cov.: 33 AF XY: 0.00155 AC XY: 1128 AN XY: 726992

African (AFR) AF: 0.0614 AC: 2056 AN: 33472

American (AMR) AF: 0.00466 AC: 208 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1111806

Other (OTH) AF: 0.00437 AC: 264 AN: 60384

GnomAD4 genome AF: 0.0188 AC: 2866 AN: 152282 Hom.: 84 Cov.: 33 AF XY: 0.0182 AC XY: 1352 AN XY: 74470

African (AFR) AF: 0.0650 AC: 2701 AN: 41540

American (AMR) AF: 0.00862 AC: 132 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68028

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00160 Hom.: 1

Bravo AF: 0.0206

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.67
PhyloP100		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.040
dbscSNV1_RF	Benign	0.54
SpliceAI score (max)		0.070		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: rs10152092; hg19: chr14-24033372;