NM_032785.4:c.960C>A

Variant names:

• chr1-48590977-G-T
• rs964469836
• NM_032785.4:c.960C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032785.4(AGBL4):​c.960C>A​(p.Ser320Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,607,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: AGBL4 NM_032785.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22451144).

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.960C>A	p.Ser320Arg	missense	Exon 10 of 14	NP_116174.3	Q5VU57-1
	AGBL4	NM_001323574.2		c.996C>A	p.Ser332Arg	missense	Exon 10 of 14	NP_001310503.1
	AGBL4	NM_001323573.2		c.996C>A	p.Ser332Arg	missense	Exon 10 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.960C>A	p.Ser320Arg	missense	Exon 10 of 14	ENSP00000360905.1	Q5VU57-1
	AGBL4	ENST00000416121.5	TSL:1	c.495C>A	p.Ser165Arg	missense	Exon 6 of 7	ENSP00000401622.1	H0Y5X4

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151656 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

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: 0.00000836 AC: 2 AN: 239152 AF XY: 0.00

Gnomad AFR exome AF: 0.000136

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1456130 Hom.: 0 Cov.: 31 AF XY: 0.00000415 AC XY: 3 AN XY: 723398

African (AFR) AF: 0.000150 AC: 5 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 84378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109530

Other (OTH) AF: 0.0000166 AC: 1 AN: 60218

GnomAD4 genome AF: 0.0000396 AC: 6 AN: 151656 Hom.: 0 Cov.: 31 AF XY: 0.0000405 AC XY: 3 AN XY: 74016

African (AFR) AF: 0.000121 AC: 5 AN: 41216

American (AMR) AF: 0.0000657 AC: 1 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000450 Hom.: 0

ClinVar

ClinVar submissions as Germline

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	0.33
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.37	N
PhyloP100		2.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.22
Sift	Benign	0.46	T
Sift4G	Benign	0.52	T
Polyphen		0.034	B
Vest4		0.52
MutPred		0.62		Gain of catalytic residue at S320 (P = 0.005)
MVP		0.12
MPC		0.33
ClinPred		0.16	T
GERP RS		2.9
Varity_R		0.11
gMVP		0.28
Mutation Taster		=64/36	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: rs964469836; hg19: chr1-49056649;