chr8-116657222-G-T

Variant names:

• chr8-116657222-G-T
• rs776462055
• NM_003756.3:c.550C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003756.3(EIF3H):​c.550C>A​(p.Pro184Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,702 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. P184S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EIF3H NM_003756.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26058957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3H	NM_003756.3	c.550C>A	p.Pro184Thr	missense_variant	Exon 4 of 8	ENST00000521861.6	NP_003747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3H	ENST00000521861.6	c.550C>A	p.Pro184Thr	missense_variant	Exon 4 of 8	1	NM_003756.3	ENSP00000429931.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460702 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726734

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111064

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.33	T;.;T;T;.
Eigen	Benign	0.098
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N;.;.;.;.
PhyloP100		5.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	D;.;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.20	T;.;T;T;T
Sift4G	Benign	0.35	T;T;T;D;.
Polyphen		0.085	B;.;B;.;.
Vest4		0.70
MutPred		0.28		.;.;Gain of phosphorylation at P198 (P = 0.0469);.;.;
MVP		0.56
MPC		0.15
ClinPred		0.30	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.69
Mutation Taster		=36/64	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

dbSNP: rs776462055; hg19: chr8-117669461;