rs762472578

Variant names:

• chr2-235494722-C-T
• rs762472578
• NM_001037131.3:c.36C>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.36C>T​(p.Ala12Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000481 in 1,560,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: AGAP1 NM_001037131.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.26
• Publications: 0 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=-0.27).
• BP6: Variant 2-235494722-C-T is Benign according to our data. Variant chr2-235494722-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2054879.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.26 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.36C>T	p.Ala12Ala	synonymous	Exon 1 of 18	NP_001032208.1	Q9UPQ3-1
	AGAP1	NM_014914.5		c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 17	NP_055729.2	Q9UPQ3-2
	AGAP1	NM_001244888.2		c.36C>T	p.Ala12Ala	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.36C>T	p.Ala12Ala	synonymous	Exon 1 of 18	ENSP00000307634.7	Q9UPQ3-1
	AGAP1	ENST00000336665.9	TSL:1	c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 17	ENSP00000338378.5	Q9UPQ3-2
	AGAP1	ENST00000409457.5	TSL:1	c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 10	ENSP00000387174.1	Q9UPQ3-3

Frequencies

GnomAD3 genomes AF: 0.0000333 AC: 5 AN: 150256 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000257 AC: 54 AN: 210506 AF XY: 0.000207

Gnomad AFR exome AF: 0.0000891

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000210

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000496 AC: 70 AN: 1410078 Hom.: 0 Cov.: 31 AF XY: 0.0000513 AC XY: 36 AN XY: 701296

African (AFR) AF: 0.000138 AC: 4 AN: 29060

American (AMR) AF: 0.00152 AC: 60 AN: 39574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24424

East Asian (EAS) AF: 0.00 AC: 0 AN: 33408

South Asian (SAS) AF: 0.00 AC: 0 AN: 82448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5426

European-Non Finnish (NFE) AF: 0.00000553 AC: 6 AN: 1085848

Other (OTH) AF: 0.00 AC: 0 AN: 57746

GnomAD4 genome AF: 0.0000333 AC: 5 AN: 150256 Hom.: 0 Cov.: 29 AF XY: 0.0000273 AC XY: 2 AN XY: 73338

African (AFR) AF: 0.0000487 AC: 2 AN: 41074

American (AMR) AF: 0.000132 AC: 2 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 4982

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67464

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000155

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	-0.27
CADD	Benign	16
DANN	Uncertain	0.98
PhyloP100		3.3
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: rs762472578; hg19: chr2-236403366;