chr1-48534246-G-C

Variant names:

• chr1-48534246-G-C
• rs774502535
• NM_032785.4:c.1439C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032785.4(AGBL4):​c.1439C>G​(p.Ala480Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,399,410 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. 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. A480V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: AGBL4 NM_032785.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11975965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.1439C>G	p.Ala480Gly	missense_variant	Exon 14 of 14	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.1439C>G	p.Ala480Gly	missense_variant	Exon 14 of 14	2	NM_032785.4	ENSP00000360905.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000636 AC: 1 AN: 157212 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83146

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000164

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000336 AC: 47 AN: 1399410 Hom.: 0 Cov.: 30 AF XY: 0.0000232 AC XY: 16 AN XY: 690200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000408

Gnomad4 OTH exome AF: 0.0000517

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.0037	T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.095
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.34	N;.
REVEL	Benign	0.033
Sift	Benign	0.090	T;.
Sift4G	Benign	0.49	T;T
Polyphen		0.079	B;.
Vest4		0.044
MutPred		0.28		Gain of loop (P = 0.024);.;
MVP		0.11
MPC		0.13
ClinPred		0.17	T
GERP RS		4.0
Varity_R		0.075
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs774502535; hg19: chr1-48999918;