1-23431103-G-C

Variant names:

• chr1-23431103-G-C
• rs200734272
• NM_017707.4:c.2569C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017707.4(ASAP3):​c.2569C>G​(p.Arg857Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R857W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASAP3 NM_017707.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 2 publications found

Genes affected

ASAP3 (HGNC:14987): (ArfGAP with SH3 domain, ankyrin repeat and PH domain 3) This gene encodes a member of a subfamily of ADP-ribosylation factor(Arf) GTPase-activating proteins that contain additional ankyrin repeat and pleckstrin homology domains. The Arf GAP domain of this protein catalyzes the hydrolysis of GTP bound to Arf proteins. The encoded protein promotes cell differentiation and migration and has been implicated in cancer cell invasion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.272228).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017707.4. 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
	ASAP3	NM_017707.4	MANE Select	c.2569C>G	p.Arg857Gly	missense	Exon 24 of 25	NP_060177.2
	ASAP3	NM_001143778.2		c.2542C>G	p.Arg848Gly	missense	Exon 23 of 24	NP_001137250.1	Q8TDY4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAP3	ENST00000336689.8	TSL:1 MANE Select	c.2569C>G	p.Arg857Gly	missense	Exon 24 of 25	ENSP00000338769.3	Q8TDY4-1
	ASAP3	ENST00000948796.1		c.2638C>G	p.Arg880Gly	missense	Exon 24 of 25	ENSP00000618855.1
	ASAP3	ENST00000857995.1		c.2632C>G	p.Arg878Gly	missense	Exon 24 of 25	ENSP00000528054.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1439622 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713864

African (AFR) AF: 0.00 AC: 0 AN: 33158

American (AMR) AF: 0.00 AC: 0 AN: 41098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25546

East Asian (EAS) AF: 0.00 AC: 0 AN: 38804

South Asian (SAS) AF: 0.00 AC: 0 AN: 82252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101862

Other (OTH) AF: 0.00 AC: 0 AN: 59560

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Benign	0.065
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.18		Loss of methylation at R857 (P = 0.0332)
MVP		0.76
MPC		0.67
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.23
gMVP		0.44
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs200734272; hg19: chr1-23757596;