1-48653385-T-C

Variant names:

• chr1-48653385-T-C
• rs764317600
• NM_032785.4:c.791A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032785.4(AGBL4):​c.791A>G​(p.Lys264Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000557 in 1,436,902 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: AGBL4 NM_032785.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

Genes affected

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032785.4. 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
	AGBL4	NM_032785.4	MANE Select	c.791A>G	p.Lys264Arg	missense	Exon 8 of 14	NP_116174.3	Q5VU57-1
	AGBL4	NM_001323574.2		c.827A>G	p.Lys276Arg	missense	Exon 8 of 14	NP_001310503.1
	AGBL4	NM_001323573.2		c.827A>G	p.Lys276Arg	missense	Exon 8 of 13	NP_001310502.1	Q5VU57-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.791A>G	p.Lys264Arg	missense	Exon 8 of 14	ENSP00000360905.1	Q5VU57-1
	AGBL4	ENST00000416121.5	TSL:1	c.326A>G	p.Lys109Arg	missense	Exon 4 of 7	ENSP00000401622.1	H0Y5X4
	AGBL4	ENST00000371838.5	TSL:5	c.791A>G	p.Lys264Arg	missense	Exon 8 of 9	ENSP00000360904.1	B1AMW3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000945 AC: 2 AN: 211638 AF XY: 0.0000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000642

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000557 AC: 8 AN: 1436902 Hom.: 0 Cov.: 30 AF XY: 0.00000984 AC XY: 7 AN XY: 711720

African (AFR) AF: 0.00 AC: 0 AN: 33046

American (AMR) AF: 0.00 AC: 0 AN: 41484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25564

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38788

South Asian (SAS) AF: 0.00 AC: 0 AN: 81604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000546 AC: 6 AN: 1099072

Other (OTH) AF: 0.0000168 AC: 1 AN: 59622

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000831 AC: 1

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	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	-0.098	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.38
Sift	Benign	0.052	T
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.65		Loss of methylation at K264 (P = 0.0238)
MVP		0.20
MPC		0.54
ClinPred		0.77	D
GERP RS		5.8
Varity_R		0.35
gMVP		0.71
Mutation Taster		=205/95	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: rs764317600; hg19: chr1-49119057;