chr15-44537347-G-T

Variant names:

• chr15-44537347-G-T
• rs559737495
• NM_003758.4:c.67G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003758.4(EIF3J):​c.67G>T​(p.Asp23Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,414,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D23N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EIF3J NM_003758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37899363).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003758.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3J	NM_003758.4	MANE Select	c.67G>T	p.Asp23Tyr	missense	Exon 2 of 8	NP_003749.2	O75822-1
	EIF3J	NM_001284336.2		c.67G>T	p.Asp23Tyr	missense	Exon 2 of 6	NP_001271265.1	O75822-3
	EIF3J	NM_001284335.2		c.67G>T	p.Asp23Tyr	missense	Exon 2 of 7	NP_001271264.1	O75822-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3J	ENST00000261868.10	TSL:1 MANE Select	c.67G>T	p.Asp23Tyr	missense	Exon 2 of 8	ENSP00000261868.5	O75822-1
	EIF3J	ENST00000424492.7	TSL:4	c.67G>T	p.Asp23Tyr	missense	Exon 2 of 6	ENSP00000414548.3	O75822-3
	EIF3J	ENST00000535391.5	TSL:2	c.67G>T	p.Asp23Tyr	missense	Exon 2 of 7	ENSP00000440221.1	O75822-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000579 AC: 1 AN: 172824 AF XY: 0.0000108

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000143

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1414328 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 699076

African (AFR) AF: 0.00 AC: 0 AN: 32450

American (AMR) AF: 0.00 AC: 0 AN: 37510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25334

East Asian (EAS) AF: 0.00 AC: 0 AN: 37270

South Asian (SAS) AF: 0.00 AC: 0 AN: 80842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1087538

Other (OTH) AF: 0.00 AC: 0 AN: 58576

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Benign	0.88
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.5
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Benign	0.033	D
Sift4G	Uncertain	0.032	D
Polyphen		0.84	P
Vest4		0.35
MutPred		0.47		Gain of sheet (P = 0.0043)
MVP		0.17
MPC		0.41
ClinPred		0.89	D
GERP RS		4.4
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.34
gMVP		0.070
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs559737495; hg19: chr15-44829545;