rs117732894

Variant names:

• chr7-134993576-C-T
• rs117732894
• NM_178563.4:c.208C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001345851.1(AGBL3):​c.-208C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,551,844 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (73 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: 2.03
• Publications: 7 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010233521).
• BP6: Variant 7-134993576-C-T is Benign according to our data. Variant chr7-134993576-C-T is described in ClinVar as Benign. ClinVar VariationId is 783007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.208C>T	p.Arg70Cys	missense	Exon 4 of 17	NP_848658.3	Q8NEM8-4
	AGBL3	NM_001345851.1		c.-208C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	NP_001332780.1
	AGBL3	NM_001367812.1		c.208C>T	p.Arg70Cys	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.208C>T	p.Arg70Cys	missense	Exon 4 of 17	ENSP00000388275.2	Q8NEM8-4
	AGBL3	ENST00000275763.10	TSL:1	n.208C>T		non_coding_transcript_exon	Exon 4 of 17	ENSP00000275763.6	Q8NEM8-2
	AGBL3	ENST00000435976.6	TSL:5	c.208C>T	p.Arg70Cys	missense	Exon 4 of 16	ENSP00000401220.2	F8W7R4

Frequencies

GnomAD3 genomes AF: 0.00623 AC: 948 AN: 152114 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00774

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00533 AC: 842 AN: 158014 AF XY: 0.00532

Gnomad AFR exome AF: 0.00134

Gnomad AMR exome AF: 0.000971

Gnomad ASJ exome AF: 0.000234

Gnomad EAS exome AF: 0.000275

Gnomad FIN exome AF: 0.00768

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00291

GnomAD4 exome AF: 0.00880 AC: 12323 AN: 1399612 Hom.: 73 Cov.: 32 AF XY: 0.00854 AC XY: 5896 AN XY: 690292

African (AFR) AF: 0.00149 AC: 47 AN: 31594

American (AMR) AF: 0.00120 AC: 43 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.000238 AC: 6 AN: 25180

East Asian (EAS) AF: 0.0000840 AC: 3 AN: 35730

South Asian (SAS) AF: 0.00109 AC: 86 AN: 79234

European-Finnish (FIN) AF: 0.00757 AC: 374 AN: 49388

Middle Eastern (MID) AF: 0.000526 AC: 3 AN: 5702

European-Non Finnish (NFE) AF: 0.0106 AC: 11421 AN: 1078972

Other (OTH) AF: 0.00585 AC: 340 AN: 58108

GnomAD4 genome AF: 0.00623 AC: 948 AN: 152232 Hom.: 5 Cov.: 32 AF XY: 0.00595 AC XY: 443 AN XY: 74444

African (AFR) AF: 0.00200 AC: 83 AN: 41538

American (AMR) AF: 0.00118 AC: 18 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4820

European-Finnish (FIN) AF: 0.00774 AC: 82 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 751 AN: 68008

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00835 Hom.: 12

Bravo AF: 0.00544

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.00145 AC: 2

ESP6500EA AF: 0.00880 AC: 28

ExAC AF: 0.00410 AC: 105

Asia WGS AF: 0.00115 AC: 4 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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.50
MVP		0.36
ClinPred		0.036	T
GERP RS		4.9
gMVP		0.62
Mutation Taster		=92/8	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: rs117732894; hg19: chr7-134678327;