2-235494793-G-T

Variant names:

• chr2-235494793-G-T
• NM_001037131.3:c.107G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001037131.3(AGAP1):​c.107G>T​(p.Arg36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.0e-7 (0 hom.)
• Consequence: AGAP1 NM_001037131.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2720203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP1	NM_001037131.3	c.107G>T	p.Arg36Leu	missense_variant	Exon 1 of 18	ENST00000304032.13	NP_001032208.1
AGAP1	NM_014914.5	c.107G>T	p.Arg36Leu	missense_variant	Exon 1 of 17		NP_055729.2
AGAP1	NM_001244888.2	c.107G>T	p.Arg36Leu	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.107G>T	p.Arg36Leu	missense_variant	Exon 1 of 18	5	NM_001037131.3	ENSP00000307634.7

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433402 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713122

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: 9.11e-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	0.22
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	-0.085	N;N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.017, 0.50	.;B;P
Vest4		0.26
MutPred		0.37		Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP		0.81
MPC		0.65
ClinPred		0.88	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-236403437;