chr10-45826177-A-G

Variant names:

• chr10-45826177-A-G
• NM_001276343.3:c.1799T>C

Variant summary

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

The NM_001276343.3(AGAP4):​c.1799T>C​(p.Leu600Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 19)
• Consequence: AGAP4 NM_001276343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64

Genes affected

AGAP4 (HGNC:23459): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 4) 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]

PARGP1-AGAP4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP4	NM_001276343.3	c.1799T>C	p.Leu600Pro	missense_variant	Exon 8 of 8	ENST00000616763.6	NP_001263272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP4	ENST00000616763.6	c.1799T>C	p.Leu600Pro	missense_variant	Exon 8 of 8	1	NM_001276343.3	ENSP00000483751.2
AGAP4	ENST00000448048.7	c.1730T>C	p.Leu577Pro	missense_variant	Exon 7 of 7	1		ENSP00000392513.2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1730T>C (p.L577P) alteration is located in exon 7 (coding exon 7) of the AGAP8 gene. This alteration results from a T to C substitution at nucleotide position 1730, causing the leucine (L) at amino acid position 577 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.055	T;.;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.3	L;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.6	D;.;.;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.012	D;.;.;.
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.76
MVP		0.43
ClinPred		0.96	D
Varity_R		0.73
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-46321625;