chr8-116646488-T-C

Variant names:

• chr8-116646488-T-C
• NM_003756.3:c.944A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003756.3(EIF3H):​c.944A>G​(p.Asp315Gly) variant causes a missense change involving the alteration of a 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: EIF3H NM_003756.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3H	NM_003756.3	c.944A>G	p.Asp315Gly	missense_variant	Exon 7 of 8	ENST00000521861.6	NP_003747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3H	ENST00000521861.6	c.944A>G	p.Asp315Gly	missense_variant	Exon 7 of 8	1	NM_003756.3	ENSP00000429931.1
EIF3H	ENST00000276682.8	c.986A>G	p.Asp329Gly	missense_variant	Exon 9 of 10	2		ENSP00000276682.4
EIF3H	ENST00000520289.1	n.*93A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.944A>G (p.D315G) alteration is located in exon 7 (coding exon 7) of the EIF3H gene. This alteration results from a A to G substitution at nucleotide position 944, causing the aspartic acid (D) at amino acid position 315 to be replaced by a glycine (G). 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	0.81
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;.;T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L;.;.
PhyloP100		8.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.8	D;.;D
REVEL	Benign	0.24
Sift	Benign	0.030	D;.;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0040	B;.;B
Vest4		0.81
MutPred		0.29		.;.;Gain of catalytic residue at P325 (P = 0.1102);
MVP		0.70
MPC		0.13
ClinPred		0.95	D
GERP RS		6.0
Varity_R		0.33
gMVP		0.68
Mutation Taster		=48/52	disease causing

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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Other links and lift over

hg19: chr8-117658727;