rs773938960

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-135032895-C-A
• chr7-135032895-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178563.4(AGBL3):​c.470C>A​(p.Pro157His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P157L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGBL3 NM_178563.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2776134).

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>A	p.Pro157His	missense	Exon 6 of 17	NP_848658.3	Q8NEM8-4
	AGBL3	NM_001345850.1		c.4-11130C>A		intron	N/A	NP_001332779.1
	AGBL3	NM_001345851.1		c.4-11130C>A		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>A	p.Pro157His	missense	Exon 6 of 17	ENSP00000388275.2	Q8NEM8-4
	AGBL3	ENST00000275763.10	TSL:1	n.470C>A		non_coding_transcript_exon	Exon 6 of 17	ENSP00000275763.6	Q8NEM8-2
	AGBL3	ENST00000435976.6	TSL:5	c.470C>A	p.Pro157His	missense	Exon 6 of 16	ENSP00000401220.2	F8W7R4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399186 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 1078826

Other (OTH) AF: 0.00 AC: 0 AN: 58048

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000399 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.7
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.21
Sift	Uncertain	0.015	D
Sift4G	Benign	0.073	T
Polyphen		0.94	P
Vest4		0.40
MutPred		0.54		Loss of phosphorylation at T156 (P = 0.072)
MVP		0.21
ClinPred		0.94	D
GERP RS		4.2
gMVP		0.36
Mutation Taster		=85/15	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;