rs186048202

Variant names:

• chr7-134993522-C-T
• rs186048202
• NM_178563.4:c.154C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001345851.1(AGBL3):​c.-262C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00241 in 1,548,150 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (107 hom.)
• Consequence: AGBL3 NM_001345851.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.55
• Publications: 3 publications found

Genes affected

AGBL3 (HGNC:27981): (AGBL carboxypeptidase 3) Enables metallocarboxypeptidase activity. Involved in protein side chain deglutamylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286458 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003987968).
• BP6: Variant 7-134993522-C-T is Benign according to our data. Variant chr7-134993522-C-T is described in ClinVar as Benign. ClinVar VariationId is 769734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001345851.1. 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
	AGBL3	NM_178563.4	MANE Select	c.154C>T	p.Arg52Trp	missense	Exon 4 of 17	NP_848658.3	Q8NEM8-4
	AGBL3	NM_001345851.1		c.-262C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	NP_001332780.1
	AGBL3	NM_001367812.1		c.154C>T	p.Arg52Trp	missense	Exon 4 of 5	NP_001354741.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL3	ENST00000436302.6	TSL:2 MANE Select	c.154C>T	p.Arg52Trp	missense	Exon 4 of 17	ENSP00000388275.2	Q8NEM8-4
	AGBL3	ENST00000275763.10	TSL:1	n.154C>T		non_coding_transcript_exon	Exon 4 of 17	ENSP00000275763.6	Q8NEM8-2
	AGBL3	ENST00000435976.6	TSL:5	c.154C>T	p.Arg52Trp	missense	Exon 4 of 16	ENSP00000401220.2	F8W7R4

Frequencies

GnomAD3 genomes AF: 0.00647 AC: 980 AN: 151582 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0600

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: 0.0000442

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.0108 AC: 1665 AN: 154794 AF XY: 0.00811

Gnomad AFR exome AF: 0.000879

Gnomad AMR exome AF: 0.0675

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00783

GnomAD4 exome AF: 0.00196 AC: 2735 AN: 1396450 Hom.: 107 Cov.: 32 AF XY: 0.00170 AC XY: 1171 AN XY: 688562

African (AFR) AF: 0.000539 AC: 17 AN: 31512

American (AMR) AF: 0.0704 AC: 2481 AN: 35224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25104

East Asian (EAS) AF: 0.00 AC: 0 AN: 35642

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.0000455 AC: 49 AN: 1077722

Other (OTH) AF: 0.00323 AC: 187 AN: 57900

GnomAD4 genome AF: 0.00660 AC: 1001 AN: 151700 Hom.: 34 Cov.: 32 AF XY: 0.00743 AC XY: 551 AN XY: 74160

African (AFR) AF: 0.00102 AC: 42 AN: 41320

American (AMR) AF: 0.0613 AC: 935 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67898

Other (OTH) AF: 0.0100 AC: 21 AN: 2098

Alfa AF: 0.00121 Hom.: 10

Bravo AF: 0.0104

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00146 AC: 37

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.5
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.57
ClinPred		0.10	T
GERP RS		5.7
gMVP		0.63
Mutation Taster		=86/14	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs186048202; hg19: chr7-134678273;