Variant 22-36519533-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003753.4(EIF3D):c.583T>C(p.Cys195Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

EIF3D
NM_003753.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.96

Variant links:

Genes affected

EIF3D (HGNC:3278): (eukaryotic translation initiation factor 3 subunit D) Eukaryotic translation initiation factor-3 (eIF3), the largest of the eIFs, is a multiprotein complex composed of at least ten nonidentical subunits. The complex binds to the 40S ribosome and helps maintain the 40S and 60S ribosomal subunits in a dissociated state. It is also thought to play a role in the formation of the 40S initiation complex by interacting with the ternary complex of eIF2/GTP/methionyl-tRNA, and by promoting mRNA binding. The protein encoded by this gene is the major RNA binding subunit of the eIF3 complex. [provided by RefSeq, Jul 2008]

EIF3D links:

EIF3D (HGNC:):

EIF3D links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41857815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3D	NM_003753.4 linkuse as main transcript	c.583T>C	p.Cys195Arg	missense_variant	8/15	ENST00000216190.13	NP_003744.1	O15371-1
EIF3D	XM_047441560.1 linkuse as main transcript	c.583T>C	p.Cys195Arg	missense_variant	8/10		XP_047297516.1
EIF3D	NR_156418.2 linkuse as main transcript	n.684T>C		non_coding_transcript_exon_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EIF3D	ENST00000216190.13 linkuse as main transcript	c.583T>C	p.Cys195Arg	missense_variant	8/15	1	NM_003753.4	ENSP00000216190.8	O15371-1
EIF3D	ENST00000405442.5 linkuse as main transcript	c.583T>C	p.Cys195Arg	missense_variant	8/15	5		ENSP00000385812.1	O15371-1
EIF3D	ENST00000455547.5 linkuse as main transcript	c.583T>C	p.Cys195Arg	missense_variant	9/10	5		ENSP00000390438.1	B0QYA5
EIF3D	ENST00000458572.1 linkuse as main transcript	n.-33T>C		upstream_gene_variant		3		ENSP00000391061.2	B0QYA4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151888

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.583T>C (p.C195R) alteration is located in exon 8 (coding exon 7) of the EIF3D gene. This alteration results from a T to C substitution at nucleotide position 583, causing the cysteine (C) at amino acid position 195 to be replaced by an arginine (R). 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

Uncertain

0.40

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.071

T;T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.090

N;N;.

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.51

Sift

Benign

0.55

T;T;T

Sift4G

Benign

0.61

T;T;.

Polyphen

0.025

B;B;.

Vest4

0.95

MutPred

0.48

Gain of disorder (P = 0.0376);Gain of disorder (P = 0.0376);Gain of disorder (P = 0.0376);

MVP

0.59

MPC

1.6

ClinPred

0.82

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over