rs367831435

Variant names:

• chr1-48590867-T-A
• NM_032785.4:c.1070A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-48590867-T-A
• chr1-48590867-T-C

Variant summary

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

The NM_032785.4(AGBL4):​c.1070A>T​(p.Lys357Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. K357R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AGBL4 NM_032785.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.1070A>T	p.Lys357Met	missense_variant	Exon 10 of 14	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.1070A>T	p.Lys357Met	missense_variant	Exon 10 of 14	2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000416121.5	c.605A>T	p.Lys202Met	missense_variant	Exon 6 of 7	1		ENSP00000401622.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453150 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721636

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: 9.03e-7

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	0.63
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.3	D;.
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.016	D;D
Polyphen		1.0	D;.
Vest4		0.54
MutPred		0.69		Loss of ubiquitination at K357 (P = 0.0174);.;
MVP		0.25
MPC		0.67
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.49
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-49056539;