1-23431757-A-G

Variant names:

• chr1-23431757-A-G
• rs775080630
• NM_017707.4:c.2485T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017707.4(ASAP3):​c.2485T>C​(p.Ser829Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,376,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. S829T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ASAP3 NM_017707.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.105459124).

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.2485T>C	p.Ser829Pro	missense	Exon 23 of 25	NP_060177.2
	ASAP3	NM_001143778.2		c.2458T>C	p.Ser820Pro	missense	Exon 22 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.2485T>C	p.Ser829Pro	missense	Exon 23 of 25	ENSP00000338769.3	Q8TDY4-1
	ASAP3	ENST00000948796.1		c.2554T>C	p.Ser852Pro	missense	Exon 23 of 25	ENSP00000618855.1
	ASAP3	ENST00000857995.1		c.2548T>C	p.Ser850Pro	missense	Exon 23 of 25	ENSP00000528054.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000563 AC: 1 AN: 177524 AF XY: 0.0000106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376374 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 678298

African (AFR) AF: 0.00 AC: 0 AN: 29684

American (AMR) AF: 0.00 AC: 0 AN: 28934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20422

East Asian (EAS) AF: 0.00 AC: 0 AN: 38012

South Asian (SAS) AF: 0.00 AC: 0 AN: 71520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4752

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076130

Other (OTH) AF: 0.00 AC: 0 AN: 56576

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.073	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.59
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.022	D
Polyphen		0.61	P
Vest4		0.28
MutPred		0.13		Loss of phosphorylation at S829 (P = 0.0031)
MVP		0.34
MPC		0.28
ClinPred		0.26	T
GERP RS		2.5
Varity_R		0.077
gMVP		0.17
Mutation Taster		=80/20	polymorphism

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: rs775080630; hg19: chr1-23758250;