chr1-23431093-G-C

Variant names:

• chr1-23431093-G-C
• rs749012817
• NM_017707.4:c.2579C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017707.4(ASAP3):​c.2579C>G​(p.Ala860Gly) 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. 16/22 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. A860T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASAP3 NM_017707.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022062927).

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.2579C>G	p.Ala860Gly	missense	Exon 24 of 25	NP_060177.2
	ASAP3	NM_001143778.2		c.2552C>G	p.Ala851Gly	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.2579C>G	p.Ala860Gly	missense	Exon 24 of 25	ENSP00000338769.3	Q8TDY4-1
	ASAP3	ENST00000948796.1		c.2648C>G	p.Ala883Gly	missense	Exon 24 of 25	ENSP00000618855.1
	ASAP3	ENST00000857995.1		c.2642C>G	p.Ala881Gly	missense	Exon 24 of 25	ENSP00000528054.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000782 AC: 12 AN: 153356 AF XY: 0.0000729

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000259

Gnomad FIN exome AF: 0.000223

Gnomad NFE exome AF: 0.000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000143 AC: 20 AN: 1400640 Hom.: 0 Cov.: 31 AF XY: 0.0000116 AC XY: 8 AN XY: 691542

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31952

American (AMR) AF: 0.00 AC: 0 AN: 36216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25056

East Asian (EAS) AF: 0.0000823 AC: 3 AN: 36444

South Asian (SAS) AF: 0.00 AC: 0 AN: 79348

European-Finnish (FIN) AF: 0.0000639 AC: 3 AN: 46938

Middle Eastern (MID) AF: 0.00260 AC: 12 AN: 4616

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1082020

Other (OTH) AF: 0.00 AC: 0 AN: 58050

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.29
DANN	Benign	0.25
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0043	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.49	N
PhyloP100		-1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.078
Sift	Benign	0.61	T
Sift4G	Benign	0.97	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.061
MPC		0.22
ClinPred		0.0091	T
GERP RS		-4.4
Varity_R		0.016
gMVP		0.13
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs749012817; hg19: chr1-23757586; COSMIC: COSV60872873; COSMIC: COSV60872873;