rs367817872

Variant names:

• chr11-72704310-C-A
• NM_001040118.3:c.1834G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-72704310-C-A
• chr11-72704310-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040118.3(ARAP1):​c.1834G>T​(p.Ala612Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARAP1 NM_001040118.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

Genes affected

ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ARAP1-AS2 (HGNC:39994): (ARAP1 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13505957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAP1	NM_001040118.3	c.1834G>T	p.Ala612Ser	missense_variant	Exon 14 of 35	ENST00000393609.8	NP_001035207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAP1	ENST00000393609.8	c.1834G>T	p.Ala612Ser	missense_variant	Exon 14 of 35	2	NM_001040118.3	ENSP00000377233.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446654 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718724

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	.;.;.;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	N;.;.;N;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.59	N;N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.10	T;T;T;T;T
Sift4G	Benign	0.87	T;T;T;T;T
Polyphen		0.0010	B;B;.;B;B
Vest4		0.26
MutPred		0.57		Loss of loop (P = 0.0804);.;.;Loss of loop (P = 0.0804);.;
MVP		0.24
MPC		0.38
ClinPred		0.11	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.021
gMVP		0.19

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: chr11-72415355;