NM_001077665.3:c.147A>G

Variant names:

• chr10-49988862-A-G
• rs371327390
• NM_001077665.3:c.147A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001077665.3(AGAP6):​c.147A>G​(p.Val49Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,593,090 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 0.00025 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: AGAP6 NM_001077665.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.165
• Publications: 0 publications found

Genes affected

AGAP6 (HGNC:23466): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 6) 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]

TIMM23B-AGAP6 (HGNC:45009): (TIMM23B-AGAP6 readthrough (NMD candidate)) This locus represents naturally-occurring readthrough transcription between the adjacent TIMM23B (translocase of inner mitochondrial membrane 23 homolog B) and AGAP6 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 6) genes. Readthrough transcripts contain portions of the coding sequence for both genes and are predicted to be candidates for nonsense-mediated decay (NMD). [provided by RefSeq, Sep 2018]

ENSG00000285803 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-49988862-A-G is Benign according to our data. Variant chr10-49988862-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2640466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.165 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077665.3. 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
	AGAP6	NM_001077665.3	MANE Select	c.147A>G	p.Val49Val	synonymous	Exon 1 of 8	NP_001071133.2	Q5VW22-2
	TIMM23B-AGAP6	NR_158658.1		n.910A>G		non_coding_transcript_exon	Exon 8 of 15
	TIMM23B-AGAP6	NR_158660.1		n.1093A>G		non_coding_transcript_exon	Exon 10 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP6	ENST00000412531.7	TSL:1 MANE Select	c.147A>G	p.Val49Val	synonymous	Exon 1 of 8	ENSP00000500374.1	Q5VW22-2
	AGAP6	ENST00000374056.10	TSL:1	c.147A>G	p.Val49Val	synonymous	Exon 1 of 7	ENSP00000363168.6	Q5VW22-1
	AGAP6	ENST00000311652.11	TSL:1	c.147A>G	p.Val49Val	synonymous	Exon 1 of 8	ENSP00000309985.8	A0A087WSV4

Frequencies

GnomAD3 genomes AF: 0.000262 AC: 39 AN: 149046 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000201

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.00107

Gnomad FIN AF: 0.0000974

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000254

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00146 AC: 31 AN: 21292 AF XY: 0.00110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00628

Gnomad EAS exome AF: 0.000325

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000718

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000261 AC: 377 AN: 1443942 Hom.: 1 Cov.: 78 AF XY: 0.000326 AC XY: 234 AN XY: 718880

African (AFR) AF: 0.000120 AC: 4 AN: 33384

American (AMR) AF: 0.0000895 AC: 4 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39684

South Asian (SAS) AF: 0.00147 AC: 127 AN: 86136

European-Finnish (FIN) AF: 0.000173 AC: 7 AN: 40470

Middle Eastern (MID) AF: 0.000403 AC: 2 AN: 4964

European-Non Finnish (NFE) AF: 0.000183 AC: 203 AN: 1108396

Other (OTH) AF: 0.000250 AC: 15 AN: 60094

GnomAD4 genome AF: 0.000248 AC: 37 AN: 149148 Hom.: 0 Cov.: 29 AF XY: 0.000275 AC XY: 20 AN XY: 72740

African (AFR) AF: 0.0000984 AC: 4 AN: 40644

American (AMR) AF: 0.000201 AC: 3 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00139 AC: 7 AN: 5044

South Asian (SAS) AF: 0.00107 AC: 5 AN: 4670

European-Finnish (FIN) AF: 0.0000974 AC: 1 AN: 10264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000254 AC: 17 AN: 66900

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.000474 Hom.: 0

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

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	-0.78
CADD	Benign	2.9
DANN	Benign	0.39
PhyloP100		0.17
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs371327390; hg19: chr10-51748622; COSMIC: COSV65017552;