1-49719403-A-C

Position:

• chr1-49719403-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032785.4(AGBL4):​c.158-21966T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

Genes affected

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.158-21966T>G		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.158-21966T>G		intron_variant		2	NM_032785.4	ENSP00000360905	P1
AGBL4	ENST00000371836.1	c.158-21966T>G		intron_variant		1		ENSP00000360902
AGBL4	ENST00000371838.5	c.158-21966T>G		intron_variant		5		ENSP00000360904
AGBL4	ENST00000497451.1	n.124-21966T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs11205641; hg19: chr1-50185075;