15-44557613-T-A

Variant summary

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

The NM_003758.4(EIF3J):c.534T>A(p.Ser178Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF3J NM_003758.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.291

Genes affected

EIF3J (HGNC:3270): (eukaryotic translation initiation factor 3 subunit J) This gene encodes a core subunit of the eukaryotic initiation factor 3 complex, which participates in the initiation of translation by aiding in the recruitment of protein and mRNA components to the 40S ribosome. There are pseudogenes for this gene on chromosomes 1, 3, and 9. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

SPG11 (HGNC:11226): (SPG11 vesicle trafficking associated, spatacsin) The protein encoded by this gene is a potential transmembrane protein that is phosphorylated upon DNA damage. Defects in this gene are a cause of spastic paraplegia type 11 (SPG11). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

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/exons	MANE	UniProt
EIF3J	NM_003758.4	c.534T>A	p.Ser178Arg	missense_variant	6/8	ENST00000261868.10
EIF3J	NM_001284336.2	c.387T>A	p.Ser129Arg	missense_variant	4/6
EIF3J	NM_001284335.2	c.410-2636T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF3J	ENST00000261868.10	c.534T>A	p.Ser178Arg	missense_variant	6/8	1	NM_003758.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.534T>A (p.S178R) alteration is located in exon 6 (coding exon 6) of the EIF3J gene. This alteration results from a T to A substitution at nucleotide position 534, causing the serine (S) at amino acid position 178 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	0.052
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	0.50	D;D;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.46	T;T
Sift4G	Benign	0.47	T;T
Polyphen		1.0	D;.
Vest4		0.79
MutPred		0.42		Gain of solvent accessibility (P = 0.0584);.;
MVP		0.43
MPC		1.1
ClinPred		0.93	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.53

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: chr15-44849811;