NM_001037131.3:c.109G>T

Variant names:

• chr2-235494795-G-T
• rs745570362
• NM_001037131.3:c.109G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001037131.3(AGAP1):​c.109G>T​(p.Val37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,585,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V37A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: AGAP1 NM_001037131.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.21
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12399092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037131.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP1	NM_001037131.3	MANE Select	c.109G>T	p.Val37Leu	missense	Exon 1 of 18	NP_001032208.1	Q9UPQ3-1
	AGAP1	NM_014914.5		c.109G>T	p.Val37Leu	missense	Exon 1 of 17	NP_055729.2	Q9UPQ3-2
	AGAP1	NM_001244888.2		c.109G>T	p.Val37Leu	missense	Exon 1 of 10	NP_001231817.1	Q9UPQ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP1	ENST00000304032.13	TSL:5 MANE Select	c.109G>T	p.Val37Leu	missense	Exon 1 of 18	ENSP00000307634.7	Q9UPQ3-1
	AGAP1	ENST00000336665.9	TSL:1	c.109G>T	p.Val37Leu	missense	Exon 1 of 17	ENSP00000338378.5	Q9UPQ3-2
	AGAP1	ENST00000409457.5	TSL:1	c.109G>T	p.Val37Leu	missense	Exon 1 of 10	ENSP00000387174.1	Q9UPQ3-3

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 23 AN: 151432 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000533

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000263 AC: 6 AN: 227990 AF XY: 0.00000803

Gnomad AFR exome AF: 0.000377

Gnomad AMR exome AF: 0.0000320

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000126 AC: 18 AN: 1433616 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 713254

African (AFR) AF: 0.000487 AC: 15 AN: 30802

American (AMR) AF: 0.0000239 AC: 1 AN: 41878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25202

East Asian (EAS) AF: 0.00 AC: 0 AN: 36390

South Asian (SAS) AF: 0.00 AC: 0 AN: 83696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097954

Other (OTH) AF: 0.0000338 AC: 2 AN: 59106

GnomAD4 genome AF: 0.000152 AC: 23 AN: 151432 Hom.: 0 Cov.: 29 AF XY: 0.000162 AC XY: 12 AN XY: 73964

African (AFR) AF: 0.000533 AC: 22 AN: 41308

American (AMR) AF: 0.0000657 AC: 1 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5080

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67808

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000178

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.72	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.64	N
PhyloP100		1.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.13
Sift	Benign	0.072	T
Sift4G	Benign	0.18	T
Polyphen		0.029	B
Vest4		0.13
MutPred		0.18		Gain of sheet (P = 0.0827)
MVP		0.77
MPC		0.40
ClinPred		0.037	T
GERP RS		3.3
Varity_R		0.094
gMVP		0.37
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs745570362; hg19: chr2-236403439;