10-50002009-G-C

Variant names:

• chr10-50002009-G-C
• rs782285569
• NM_001077665.3:c.410G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077665.3(AGAP6):​c.410G>C​(p.Arg137Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AGAP6 NM_001077665.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14285222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP6	NM_001077665.3	c.410G>C	p.Arg137Pro	missense_variant	Exon 5 of 8	ENST00000412531.7	NP_001071133.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP6	ENST00000412531.7	c.410G>C	p.Arg137Pro	missense_variant	Exon 5 of 8	1	NM_001077665.3	ENSP00000500374.1
TIMM23B-AGAP6	ENST00000651763.1	n.*625G>C		non_coding_transcript_exon_variant	Exon 14 of 18			ENSP00000502214.1
TIMM23B-AGAP6	ENST00000651763.1	n.*625G>C		3_prime_UTR_variant	Exon 14 of 18			ENSP00000502214.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460544 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726628

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0033	.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.47	.;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L;.
PrimateAI	Benign	0.46	T
REVEL	Benign	0.039
Sift4G	Uncertain	0.011	D;T;T
Vest4		0.35
MVP		0.17
ClinPred		0.17	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs782285569; hg19: chr10-51761769;