19-38619275-A-G

Position:

• chr19-38619275-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013234.4(EIF3K):​c.7A>G​(p.Met3Val) 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. 15/20 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: EIF3K NM_013234.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.225

Genes affected

EIF3K (HGNC:24656): (eukaryotic translation initiation factor 3 subunit K) The 700-kD eukaryotic translation initiation factor-3 (eIF3) is the largest eIF and contains at least 12 subunits, including EIF2S12. eIF3 plays an essential role in translation by binding directly to the 40S ribosomal subunit and promoting formation of the 40S preinitiation complex (Mayeur et al., 2003 [PubMed 14519125]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.121803075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3K	NM_013234.4	c.7A>G	p.Met3Val	missense_variant	1/8	ENST00000248342.9	NP_037366.1
EIF3K	NM_001300992.2	c.7A>G	p.Met3Val	missense_variant	1/7		NP_001287921.1
EIF3K	NM_001308393.2	c.-245A>G		5_prime_UTR_variant	1/8		NP_001295322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF3K	ENST00000248342.9	c.7A>G	p.Met3Val	missense_variant	1/8	1	NM_013234.4	ENSP00000248342.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2023

The c.7A>G (p.M3V) alteration is located in exon 1 (coding exon 1) of the EIF3K gene. This alteration results from a A to G substitution at nucleotide position 7, causing the methionine (M) at amino acid position 3 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	0.068
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T;T;.;.;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.28	N
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	.;L;.;L;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.3	.;N;.;N;.;.
REVEL	Benign	0.16
Sift	Benign	0.11	.;T;.;T;.;.
Sift4G	Benign	0.083	T;D;D;D;T;D
Polyphen		0.0020	.;B;.;.;.;.
Vest4		0.15
MutPred		0.30		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.32
MPC		0.38
ClinPred		0.44	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-39109915;