Genetic Variant NM_003756.3:c.901C>G (chr8-116646531-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003756.3(EIF3H):c.901C>G(p.Leu301Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EIF3H
NM_003756.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

Variant links:

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]

EIF3H links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08228418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3H	NM_003756.3 link	c.901C>G	p.Leu301Val	missense_variant	Exon 7 of 8	ENST00000521861.6	NP_003747.1	O15372Q6IB98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EIF3H	ENST00000521861.6 link	c.901C>G	p.Leu301Val	missense_variant	Exon 7 of 8	1	NM_003756.3	ENSP00000429931.1	O15372
EIF3H	ENST00000276682.8 link	c.943C>G	p.Leu315Val	missense_variant	Exon 9 of 10	2		ENSP00000276682.4	B3KS98
EIF3H	ENST00000520289.1 link	n.*50C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.901C>G (p.L301V) alteration is located in exon 7 (coding exon 7) of the EIF3H gene. This alteration results from a C to G substitution at nucleotide position 901, causing the leucine (L) at amino acid position 301 to be replaced by a valine (V). 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

0.072

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.12

DEOGEN2

Benign

0.072

T;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.0033

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.57

N;.;.

PhyloP100

2.1

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.040

N;.;N

REVEL

Benign

0.066

Sift

Benign

1.0

T;.;T

Sift4G

Benign

0.81

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.27

MutPred

0.18

.;.;Gain of glycosylation at S316 (P = 0.0902);

MVP

0.31

MPC

0.092

ClinPred

0.078

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.17

Mutation Taster

=68/32

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over