22-36519533-A-G

Position:

• chr22-36519533-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96

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]

ACMG classification

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	UniProt
EIF3D	NM_003753.4	c.583T>C	p.Cys195Arg	missense_variant	8/15	ENST00000216190.13
EIF3D	XM_047441560.1	c.583T>C	p.Cys195Arg	missense_variant	8/10
EIF3D	NR_156418.2	n.684T>C		non_coding_transcript_exon_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF3D	ENST00000216190.13	c.583T>C	p.Cys195Arg	missense_variant	8/15	1	NM_003753.4	P1
EIF3D	ENST00000405442.5	c.583T>C	p.Cys195Arg	missense_variant	8/15	5		P1
EIF3D	ENST00000455547.5	c.583T>C	p.Cys195Arg	missense_variant	9/10	5
EIF3D	ENST00000458572.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151888 Hom.: 0 Cov.: 32

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.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151888 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74178

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Benign	20
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	D
LIST_S2	Uncertain	0.88	.;D;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.090	N;N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.91	D
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	D
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

Other links and lift over

dbSNP: rs919549553; hg19: chr22-36915580;