NM_003756.3:c.70A>G

Variant names:

• chr8-116755728-T-C
• NM_003756.3:c.70A>G

Variant summary

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

The NM_003756.3(EIF3H):​c.70A>G​(p.Lys24Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF3H NM_003756.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10

Genes affected

EIF3H (HGNC:3273): (eukaryotic translation initiation factor 3 subunit H) Enables deubiquitinase activity. Contributes to translation initiation factor activity. Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process and translational initiation. Located in extracellular exosome and membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in breast cancer; prostate cancer; and prostate carcinoma. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000298999 (HGNC:):

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=0.2843577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3H	NM_003756.3	c.70A>G	p.Lys24Glu	missense_variant	Exon 1 of 8	ENST00000521861.6	NP_003747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3H	ENST00000521861.6	c.70A>G	p.Lys24Glu	missense_variant	Exon 1 of 8	1	NM_003756.3	ENSP00000429931.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.70A>G (p.K24E) alteration is located in exon 1 (coding exon 1) of the EIF3H gene. This alteration results from a A to G substitution at nucleotide position 70, causing the lysine (K) at amino acid position 24 to be replaced by a glutamic acid (E). 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	Benign	0.18
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T;.;T;.;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.78	T;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;.;.;.;.;.
PhyloP100		4.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.040	N;.;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.50	T;.;T;T;T;T
Sift4G	Benign	0.57	T;T;T;.;T;.
Polyphen		0.88	P;.;P;.;.;.
Vest4		0.65
MutPred		0.34		.;.;Loss of MoRF binding (P = 9e-04);.;.;Loss of MoRF binding (P = 9e-04);
MVP		0.55
MPC		0.13
ClinPred		0.80	D
GERP RS		5.7
PromoterAI		-0.022	Neutral
Varity_R		0.13
gMVP		0.33
Mutation Taster		=90/10	polymorphism

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

hg19: chr8-117767967; COSMIC: COSV108061526;