chr10-45825940-T-G

Variant names:

• chr10-45825940-T-G
• rs782077911
• NM_001276343.3:c.2036A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001276343.3(AGAP4):​c.2036A>C​(p.Tyr679Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,213,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000084 (0 hom., cov: 18)
  • Exomes 𝑓: 0.000011 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGAP4 NM_001276343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.59
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18247357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276343.3. 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
	AGAP4	NM_001276343.3	MANE Select	c.2036A>C	p.Tyr679Ser	missense	Exon 8 of 8	NP_001263272.2	A0A087X0Z1
	AGAP4	NM_133446.4		c.1967A>C	p.Tyr656Ser	missense	Exon 7 of 7	NP_597703.2	Q96P64
	AGAP4	NM_001393377.1		c.1919A>C	p.Tyr640Ser	missense	Exon 10 of 10	NP_001380306.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP4	ENST00000616763.6	TSL:1 MANE Select	c.2036A>C	p.Tyr679Ser	missense	Exon 8 of 8	ENSP00000483751.2	A0A087X0Z1
	AGAP4	ENST00000448048.7	TSL:1	c.1967A>C	p.Tyr656Ser	missense	Exon 7 of 7	ENSP00000392513.2	Q96P64
	AGAP4	ENST00000970389.1		c.2030A>C	p.Tyr677Ser	missense	Exon 8 of 8	ENSP00000640448.1

Frequencies

GnomAD3 genomes AF: 0.00000839 AC: 1 AN: 119166 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000795

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000596 AC: 12 AN: 201248 AF XY: 0.0000562

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000279

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: 0.000605

GnomAD4 exome AF: 0.0000107 AC: 13 AN: 1213886 Hom.: 1 Cov.: 30 AF XY: 0.00000996 AC XY: 6 AN XY: 602226

African (AFR) AF: 0.00 AC: 0 AN: 29834

American (AMR) AF: 0.000310 AC: 13 AN: 42002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22150

East Asian (EAS) AF: 0.00 AC: 0 AN: 31602

South Asian (SAS) AF: 0.00 AC: 0 AN: 62378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3384

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 927672

Other (OTH) AF: 0.00 AC: 0 AN: 50454

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000839 AC: 1 AN: 119166 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 57166

African (AFR) AF: 0.00 AC: 0 AN: 33902

American (AMR) AF: 0.0000795 AC: 1 AN: 12576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2780

East Asian (EAS) AF: 0.00 AC: 0 AN: 3700

South Asian (SAS) AF: 0.00 AC: 0 AN: 2372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53512

Other (OTH) AF: 0.00 AC: 0 AN: 1564

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000195 AC: 2

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	0.32
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.55
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.34	N
PhyloP100		5.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.27
Sift	Benign	0.29	T
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.55		Gain of glycosylation at Y656 (P = 0.0103)
MVP		0.40
ClinPred		0.23	T
Varity_R		0.37
gMVP		0.074
Mutation Taster		=99/1	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: rs782077911; hg19: chr10-46321388;