chr10-47503383-C-A

Variant names:

• chr10-47503383-C-A
• rs1270131442
• NM_001190810.1:c.746G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001190810.1(AGAP9):​c.746G>T​(p.Arg249Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (11 hom., cov: 26)
  • Exomes 𝑓: 0.00012 (13 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGAP9 NM_001190810.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

Genes affected

AGAP9 (HGNC:23463): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 9) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANXA8 (HGNC:546): (annexin A8) This gene encodes a member of the annexin family of evolutionarily conserved Ca2+ and phospholipid binding proteins. The encoded protein may function as an an anticoagulant that indirectly inhibits the thromboplastin-specific complex. Overexpression of this gene has been associated with acute myelocytic leukemia. A highly similar duplicated copy of this gene is found in close proximity on the long arm of chromosome 10. [provided by RefSeq, Jul 2008]

ENSG00000224919 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30863857).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190810.1. 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
	AGAP9	NM_001190810.1	MANE Select	c.746G>T	p.Arg249Leu	missense	Exon 8 of 8	NP_001177739.1	Q5VTM2-2
	BMS1P2-AGAP9	NR_160414.1		n.1804G>T		non_coding_transcript_exon	Exon 16 of 16
	BMS1P2-AGAP9	NR_160415.1		n.2161G>T		non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP9	ENST00000452145.6	TSL:1 MANE Select	c.746G>T	p.Arg249Leu	missense	Exon 8 of 8	ENSP00000392206.2	Q5VTM2-2
	ENSG00000224919	ENST00000434533.2	TSL:5	n.1637C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000775 AC: 115 AN: 148434 Hom.: 10 Cov.: 26

Gnomad AFR AF: 0.00286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000136 AC: 1 AN: 73398 AF XY: 0.0000277

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000125 AC: 182 AN: 1461280 Hom.: 13 Cov.: 33 AF XY: 0.0000990 AC XY: 72 AN XY: 726944

African (AFR) AF: 0.00429 AC: 142 AN: 33136

American (AMR) AF: 0.000157 AC: 7 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111880

Other (OTH) AF: 0.000331 AC: 20 AN: 60348

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000788 AC: 117 AN: 148542 Hom.: 11 Cov.: 26 AF XY: 0.000745 AC XY: 54 AN XY: 72520

African (AFR) AF: 0.00291 AC: 114 AN: 39206

American (AMR) AF: 0.000134 AC: 2 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 4952

South Asian (SAS) AF: 0.00 AC: 0 AN: 4688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67726

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000948

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	18
DANN	Benign	0.74
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.31	T
PhyloP100		1.7
PROVEAN	Pathogenic	-5.1	D
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.29
MVP		0.57
GERP RS		0.11
gMVP		0.059

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1270131442; hg19: chr10-48902730;