rs200780955

Variant names:

• chr14-23562058-C-T
• rs200780955
• NM_003917.5:c.1637G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-23562058-C-T
• chr14-23562058-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003917.5(AP1G2):​c.1637G>A​(p.Arg546His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,613,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: AP1G2 NM_003917.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15513757).

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.1637G>A	p.Arg546His	missense	Exon 17 of 22	NP_003908.1	O75843
	AP1G2	NM_001282475.2		c.1421G>A	p.Arg474His	missense	Exon 15 of 20	NP_001269404.1
	AP1G2	NM_001354673.2		c.1250G>A	p.Arg417His	missense	Exon 16 of 21	NP_001341602.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1G2	ENST00000397120.8	TSL:1 MANE Select	c.1637G>A	p.Arg546His	missense	Exon 17 of 22	ENSP00000380309.3	O75843
	AP1G2	ENST00000308724.9	TSL:1	c.1637G>A	p.Arg546His	missense	Exon 16 of 21	ENSP00000312442.5	O75843
	AP1G2	ENST00000460049.6	TSL:1	n.1810G>A		non_coding_transcript_exon	Exon 15 of 20

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000201 AC: 50 AN: 249244 AF XY: 0.000215

Gnomad AFR exome AF: 0.000311

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000302

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000272 AC: 397 AN: 1461134 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 176 AN XY: 726834

African (AFR) AF: 0.000120 AC: 4 AN: 33456

American (AMR) AF: 0.000224 AC: 10 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86144

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53298

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5644

European-Non Finnish (NFE) AF: 0.000330 AC: 367 AN: 1111786

Other (OTH) AF: 0.000133 AC: 8 AN: 60344

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74472

African (AFR) AF: 0.000313 AC: 13 AN: 41558

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000255 Hom.: 0

Bravo AF: 0.000291

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000247 AC: 30

EpiCase AF: 0.000327

EpiControl AF: 0.000713

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.3
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.11
Sift	Benign	0.044	D
Sift4G	Uncertain	0.041	D
Polyphen		0.12	B
Vest4		0.38
MVP		0.16
MPC		0.58
ClinPred		0.097	T
GERP RS		4.9
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.45
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs200780955; hg19: chr14-24031267; COSMIC: COSV55340001; COSMIC: COSV55340001;