rs144345823

Variant names:

• chr2-235494842-C-T
• rs144345823
• NM_001037131.3:c.156C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001037131.3(AGAP1):​c.156C>T​(p.Ala52Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000421 in 1,569,838 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00044 (1 hom.)
• Consequence: AGAP1 NM_001037131.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.75
• Publications: 1 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 2-235494842-C-T is Benign according to our data. Variant chr2-235494842-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2060668.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.75 with no splicing effect.

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.156C>T	p.Ala52Ala	synonymous	Exon 1 of 18	NP_001032208.1	Q9UPQ3-1
	AGAP1	NM_014914.5		c.156C>T	p.Ala52Ala	synonymous	Exon 1 of 17	NP_055729.2	Q9UPQ3-2
	AGAP1	NM_001244888.2		c.156C>T	p.Ala52Ala	synonymous	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.156C>T	p.Ala52Ala	synonymous	Exon 1 of 18	ENSP00000307634.7	Q9UPQ3-1
	AGAP1	ENST00000336665.9	TSL:1	c.156C>T	p.Ala52Ala	synonymous	Exon 1 of 17	ENSP00000338378.5	Q9UPQ3-2
	AGAP1	ENST00000409457.5	TSL:1	c.156C>T	p.Ala52Ala	synonymous	Exon 1 of 10	ENSP00000387174.1	Q9UPQ3-3

Frequencies

GnomAD3 genomes AF: 0.000238 AC: 36 AN: 151322 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000727

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: 0.000457

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000166 AC: 36 AN: 216442 AF XY: 0.000135

Gnomad AFR exome AF: 0.000170

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000344

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000441 AC: 625 AN: 1418516 Hom.: 1 Cov.: 32 AF XY: 0.000418 AC XY: 295 AN XY: 705628

African (AFR) AF: 0.0000676 AC: 2 AN: 29588

American (AMR) AF: 0.00 AC: 0 AN: 40178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24652

East Asian (EAS) AF: 0.00 AC: 0 AN: 34542

South Asian (SAS) AF: 0.00 AC: 0 AN: 82754

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.000563 AC: 614 AN: 1090288

Other (OTH) AF: 0.000137 AC: 8 AN: 58310

GnomAD4 genome AF: 0.000238 AC: 36 AN: 151322 Hom.: 0 Cov.: 29 AF XY: 0.000244 AC XY: 18 AN XY: 73918

African (AFR) AF: 0.0000727 AC: 3 AN: 41272

American (AMR) AF: 0.0000657 AC: 1 AN: 15210

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5058

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000457 AC: 31 AN: 67780

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.000441 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs144345823; hg19: chr2-236403486;