2-235494840-G-A

Variant names:

• chr2-235494840-G-A
• rs1255540343
• NM_001037131.3:c.154G>A

Variant summary

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

The NM_001037131.3(AGAP1):​c.154G>A​(p.Ala52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 29)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: AGAP1 NM_001037131.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

Genes affected

AGAP1 (HGNC:16922): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1) This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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=0.25977728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP1	NM_001037131.3	c.154G>A	p.Ala52Thr	missense_variant	Exon 1 of 18	ENST00000304032.13	NP_001032208.1
AGAP1	NM_014914.5	c.154G>A	p.Ala52Thr	missense_variant	Exon 1 of 17		NP_055729.2
AGAP1	NM_001244888.2	c.154G>A	p.Ala52Thr	missense_variant	Exon 1 of 10		NP_001231817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13	c.154G>A	p.Ala52Thr	missense_variant	Exon 1 of 18	5	NM_001037131.3	ENSP00000307634.7

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418086 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 705456

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: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.042
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.091	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.17, 0.10	.;B;B
Vest4		0.26
MutPred		0.20		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.76
MPC		0.44
ClinPred		0.47	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.091
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs1255540343; hg19: chr2-236403484;