7-135032895-C-T

Variant names:

• chr7-135032895-C-T
• rs773938960
• NM_178563.4:c.470C>T

Variant summary

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

The NM_178563.4(AGBL3):​c.470C>T​(p.Pro157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000935 in 1,551,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000097 (0 hom.)
• Consequence: AGBL3 NM_178563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.107685715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178563.4. 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
	AGBL3	NM_178563.4	MANE Select	c.470C>T	p.Pro157Leu	missense	Exon 6 of 17	NP_848658.3	Q8NEM8-4
	AGBL3	NM_001345850.1		c.4-11130C>T		intron	N/A	NP_001332779.1
	AGBL3	NM_001345851.1		c.4-11130C>T		intron	N/A	NP_001332780.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL3	ENST00000436302.6	TSL:2 MANE Select	c.470C>T	p.Pro157Leu	missense	Exon 6 of 17	ENSP00000388275.2	Q8NEM8-4
	AGBL3	ENST00000275763.10	TSL:1	n.470C>T		non_coding_transcript_exon	Exon 6 of 17	ENSP00000275763.6	Q8NEM8-2
	AGBL3	ENST00000435976.6	TSL:5	c.470C>T	p.Pro157Leu	missense	Exon 6 of 16	ENSP00000401220.2	F8W7R4

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152108 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000445 AC: 7 AN: 157270 AF XY: 0.0000481

Gnomad AFR exome AF: 0.00

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: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000972 AC: 136 AN: 1399186 Hom.: 0 Cov.: 30 AF XY: 0.0000855 AC XY: 59 AN XY: 690080

African (AFR) AF: 0.00 AC: 0 AN: 31566

American (AMR) AF: 0.00 AC: 0 AN: 35656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35708

South Asian (SAS) AF: 0.00 AC: 0 AN: 79168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.000119 AC: 128 AN: 1078826

Other (OTH) AF: 0.000138 AC: 8 AN: 58048

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152108 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74300

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.0000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000399 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	0.098
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.93
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.86	L
PhyloP100		2.7
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.11
Sift	Benign	0.057	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.56		Loss of disorder (P = 0.039)
MVP		0.19
ClinPred		0.35	T
GERP RS		4.2
gMVP		0.37
Mutation Taster		=89/11	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: rs773938960; hg19: chr7-134717646; COSMIC: COSV51952898;