11-47168175-A-T

Variant names:

• chr11-47168175-A-T
• NM_032389.6:c.1018T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_032389.6(ARFGAP2):​c.1018T>A​(p.Ser340Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARFGAP2 NM_032389.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58

Genes affected

ARFGAP2 (HGNC:13504): (ADP ribosylation factor GTPase activating protein 2) Predicted to enable GTPase activator activity. Predicted to be involved in COPI coating of Golgi vesicle. Located in Golgi apparatus; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000270060 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity ARFG2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26011398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFGAP2	NM_032389.6	c.1018T>A	p.Ser340Thr	missense_variant	Exon 11 of 16	ENST00000524782.6	NP_115765.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFGAP2	ENST00000524782.6	c.1018T>A	p.Ser340Thr	missense_variant	Exon 11 of 16	1	NM_032389.6	ENSP00000434442.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1018T>A (p.S340T) alteration is located in exon 11 (coding exon 11) of the ARFGAP2 gene. This alteration results from a T to A substitution at nucleotide position 1018, causing the serine (S) at amino acid position 340 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.028	.;T;T;.
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	.;.;M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.4	.;.;N;N
REVEL	Benign	0.10
Sift	Benign	0.27	.;.;T;T
Sift4G	Benign	0.50	T;T;T;.
Polyphen		0.091	.;.;B;.
Vest4		0.54
MutPred		0.22		.;.;Loss of phosphorylation at S340 (P = 0.0603);.;
MVP		0.33
MPC		0.37
ClinPred		0.67	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.15
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47189726;