NM_001037131.3:c.209C>T

Variant names:

• chr2-235709224-C-T
• rs139445824
• NM_001037131.3:c.209C>T

Variant summary

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

The NM_001037131.3(AGAP1):​c.209C>T​(p.Pro70Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,613,964 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P70P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: AGAP1 NM_001037131.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.34
• Publications: 5 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: Uncertain_significance. The variant received 0 ACMG points.

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.209C>T	p.Pro70Leu	missense	Exon 2 of 18	NP_001032208.1	Q9UPQ3-1
	AGAP1	NM_001436125.1		c.1004C>T	p.Pro335Leu	missense	Exon 2 of 18	NP_001423054.1
	AGAP1	NM_001436126.1		c.1004C>T	p.Pro335Leu	missense	Exon 2 of 17	NP_001423055.1	E7EUN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP1	ENST00000304032.13	TSL:5 MANE Select	c.209C>T	p.Pro70Leu	missense	Exon 2 of 18	ENSP00000307634.7	Q9UPQ3-1
	AGAP1	ENST00000336665.9	TSL:1	c.209C>T	p.Pro70Leu	missense	Exon 2 of 17	ENSP00000338378.5	Q9UPQ3-2
	AGAP1	ENST00000409457.5	TSL:1	c.209C>T	p.Pro70Leu	missense	Exon 2 of 10	ENSP00000387174.1	Q9UPQ3-3

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000334 AC: 84 AN: 251464 AF XY: 0.000324

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000304 AC: 445 AN: 1461860 Hom.: 1 Cov.: 31 AF XY: 0.000329 AC XY: 239 AN XY: 727238

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.000492 AC: 22 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.000487 AC: 42 AN: 86256

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53402

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000315 AC: 350 AN: 1111998

Other (OTH) AF: 0.000248 AC: 15 AN: 60396

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74286

African (AFR) AF: 0.0000241 AC: 1 AN: 41412

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000241 Hom.: 0

Bravo AF: 0.000238

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000305 AC: 37

EpiCase AF: 0.000327

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.46
Sift	Benign	0.067	T
Sift4G	Benign	0.083	T
Polyphen		1.0	D
Vest4		0.96
MVP		0.77
MPC		1.3
ClinPred		0.23	T
GERP RS		3.9
PromoterAI		-0.0040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.72
Mutation Taster		=14/86	disease causing

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: rs139445824; hg19: chr2-236617868;