rs5758972

Variant names:

• chr22-42836967-C-T
• rs5758972
• NM_014570.5:c.262-1474G>A

Variant summary

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

The NM_014570.5(ARFGAP3):​c.262-1474G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,046 control chromosomes in the GnomAD database, including 15,890 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 0.45 (15890 hom., cov: 31)
• Consequence: ARFGAP3 NM_014570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 10 publications found

Genes affected

ARFGAP3 (HGNC:661): (ADP ribosylation factor GTPase activating protein 3) The protein encoded by this gene is a GTPase-activating protein (GAP) that associates with the Golgi apparatus and regulates the early secretory pathway of proteins. The encoded protein promotes hydrolysis of ADP-ribosylation factor 1 (ARF1)-bound GTP, which is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is a prerequisite for the fusion of these vesicles with target compartments. The activity of this protein is sensitive to phospholipids. Multiple transcript variants encoding different isoforms have been found for this gene. This gene was originally known as ARFGAP1, but that is now the name of a related but different gene. [provided by RefSeq, Nov 2008]

PACSIN2 (HGNC:8571): (protein kinase C and casein kinase substrate in neurons 2) This gene is a member of the protein kinase C and casein kinase substrate in neurons family. The encoded protein is involved in linking the actin cytoskeleton with vesicle formation by regulating tubulin polymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFGAP3	NM_014570.5	c.262-1474G>A		intron_variant	Intron 3 of 15	ENST00000263245.10	NP_055385.3
ARFGAP3	NM_001142293.2	c.262-2642G>A		intron_variant	Intron 3 of 14		NP_001135765.1
ARFGAP3	XM_005261525.5	c.262-1474G>A		intron_variant	Intron 3 of 14		XP_005261582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFGAP3	ENST00000263245.10	c.262-1474G>A		intron_variant	Intron 3 of 15	1	NM_014570.5	ENSP00000263245.5

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68361 AN: 151928 Hom.: 15870 Cov.: 31

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.450 AC: 68422 AN: 152046 Hom.: 15890 Cov.: 31 AF XY: 0.443 AC XY: 32896 AN XY: 74328

African (AFR) AF: 0.480 AC: 19908 AN: 41456

American (AMR) AF: 0.426 AC: 6503 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1486 AN: 3472

East Asian (EAS) AF: 0.0844 AC: 437 AN: 5180

South Asian (SAS) AF: 0.412 AC: 1986 AN: 4816

European-Finnish (FIN) AF: 0.357 AC: 3771 AN: 10566

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.482 AC: 32798 AN: 67976

Other (OTH) AF: 0.452 AC: 954 AN: 2112

Alfa AF: 0.465 Hom.: 62586

Bravo AF: 0.451

Asia WGS AF: 0.284 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0060
DANN	Benign	0.26
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5758972; hg19: chr22-43232973;