NM_032785.4:c.1174G>T

Variant names:

• chr1-48587097-C-A
• NM_032785.4:c.1174G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032785.4(AGBL4):​c.1174G>T​(p.Asp392Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,438,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D392N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: AGBL4 NM_032785.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.1174G>T	p.Asp392Tyr	missense_variant	Exon 11 of 14	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.1174G>T	p.Asp392Tyr	missense_variant	Exon 11 of 14	2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000416121.5	c.709G>T	p.Asp237Tyr	missense_variant	Exon 7 of 7	1		ENSP00000401622.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438384 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 713026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Benign	0.29
Sift	Uncertain	0.015	D;.
Sift4G	Uncertain	0.015	D;D
Polyphen		0.91	P;.
Vest4		0.75
MutPred		0.70		Gain of catalytic residue at L387 (P = 0.1145);.;
MVP		0.28
MPC		0.61
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.37
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-49052769;