chr3-132660538-A-G

Position:

• chr3-132660538-A-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_024818.6(UBA5):​c.1A>G​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBA5 NM_024818.6 start_lost
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.92

Genes affected

UBA5 (HGNC:23230): (ubiquitin like modifier activating enzyme 5) This gene encodes a member of the E1-like ubiquitin-activating enzyme family. This protein activates ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein, via the formation of a high-energy thioester bond. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been identified on chromosome 1. [provided by RefSeq, Feb 2016]

NPHP3-ACAD11 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-132660538-A-G is Pathogenic according to our data. Variant chr3-132660538-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1686286.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBA5	NM_024818.6	c.1A>G	p.Met1?	start_lost	1/12	ENST00000356232.10
NPHP3-ACAD11	NR_037804.1	n.3996-15647T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBA5	ENST00000356232.10	c.1A>G	p.Met1?	start_lost	1/12	1	NM_024818.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 44 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;.;.
Eigen	Benign	-0.070
Eigen_PC	Benign	0.040
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	0.97	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Benign	-0.49	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PROVEAN	Benign	-0.91	N;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0080	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.077	B;.;B
Vest4		0.54
MutPred		0.97		Gain of glycosylation at S4 (P = 0.0012);Gain of glycosylation at S4 (P = 0.0012);Gain of glycosylation at S4 (P = 0.0012);
MVP		0.87
ClinPred		0.99	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.50

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: chr3-132379382;