rs10520642

Variant names:

• chr15-86856866-T-C
• rs10520642
• NM_001386094.1:c.3159-50221T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386094.1(AGBL1):​c.3159-50221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 152,340 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.018 (49 hom., cov: 33)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 1 publications found

Genes affected

AGBL1 (HGNC:26504): (AGBL carboxypeptidase 1) Polyglutamylation is a reversible posttranslational modification catalyzed by polyglutamylases that results in the addition of glutamate side chains on the modified protein. This gene encodes a glutamate decarboxylase that catalyzes the deglutamylation of polyglutamylated proteins. Mutations in this gene result in dominant late-onset Fuchs corneal dystrophy. [provided by RefSeq, Nov 2013]

AGBL1 Gene-Disease associations (from GenCC):

• Fuchs' endothelial dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• corneal dystrophy, Fuchs endothelial, 8

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.3159-50221T>C		intron_variant	Intron 22 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.3159-50221T>C		intron_variant	Intron 22 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.3222-131121T>C		intron_variant	Intron 23 of 24	5		ENSP00000413001.3
AGBL1	ENST00000681381.1	n.317+182430T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2776 AN: 152222 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0183 AC: 2793 AN: 152340 Hom.: 49 Cov.: 33 AF XY: 0.0192 AC XY: 1432 AN XY: 74500

African (AFR) AF: 0.0231 AC: 960 AN: 41580

American (AMR) AF: 0.0157 AC: 240 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5180

South Asian (SAS) AF: 0.0671 AC: 324 AN: 4826

European-Finnish (FIN) AF: 0.00640 AC: 68 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0145 AC: 989 AN: 68036

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0145 Hom.: 28

Bravo AF: 0.0176

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.088
DANN	Benign	0.69
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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: rs10520642; hg19: chr15-87400097;