rs776398717

Variant names:

• chr11-72687480-T-A
• rs776398717
• NM_001040118.3:c.4144A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-72687480-T-A
• chr11-72687480-T-C

Variant summary

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

The NM_001040118.3(ARAP1):​c.4144A>T​(p.Met1382Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M1382V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ARAP1 NM_001040118.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

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-AS1 (HGNC:39993): (ARAP1 antisense RNA 1)

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=0.19078618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAP1	NM_001040118.3	c.4144A>T	p.Met1382Leu	missense_variant	Exon 33 of 35	ENST00000393609.8	NP_001035207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAP1	ENST00000393609.8	c.4144A>T	p.Met1382Leu	missense_variant	Exon 33 of 35	2	NM_001040118.3	ENSP00000377233.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	0.00055	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.027	.;T;.;.;T;T;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	.;.;.;.;L;.;.;.
PhyloP100		3.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N;.;N;N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.29	T;.;T;T;T;T;T;T
Sift4G	Benign	0.063	T;T;T;T;T;T;T;T
Polyphen		0.019	B;.;B;.;B;B;.;.
Vest4		0.34
MutPred		0.47		.;.;.;.;Gain of sheet (P = 0.1208);.;.;.;
MVP		0.49
MPC		0.33
ClinPred		0.42	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.092
gMVP		0.42
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs776398717; hg19: chr11-72398525;