chr20-35280724-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002212.4(EIF6):c.299G>A(p.Arg100Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,613,910 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 1 hom. )
Consequence
EIF6
NM_002212.4 missense
NM_002212.4 missense
Scores
5
10
2
Clinical Significance
Conservation
PhyloP100: 7.49
Genes affected
EIF6 (HGNC:6159): (eukaryotic translation initiation factor 6) Hemidesmosomes are structures which link the basal lamina to the intermediate filament cytoskeleton. An important functional component of hemidesmosomes is the integrin beta-4 subunit (ITGB4), a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and prevent the association of the 40S and 60S ribosomal subunits. Multiple non-protein coding transcript variants and variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EIF6 | NM_002212.4 | c.299G>A | p.Arg100Gln | missense_variant | 4/7 | ENST00000374450.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF6 | ENST00000374450.8 | c.299G>A | p.Arg100Gln | missense_variant | 4/7 | 1 | NM_002212.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000164 AC: 41AN: 250438Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135440
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GnomAD4 exome AF: 0.000264 AC: 386AN: 1461626Hom.: 1 Cov.: 31 AF XY: 0.000263 AC XY: 191AN XY: 727078
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GnomAD4 genome AF: 0.000190 AC: 29AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74466
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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 | Jun 28, 2022 | The c.299G>A (p.R100Q) alteration is located in exon 3 (coding exon 3) of the EIF6 gene. This alteration results from a G to A substitution at nucleotide position 299, causing the arginine (R) at amino acid position 100 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;D;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;.
MutationTaster
Benign
D;D;D
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;.
Polyphen
D;D;.
Vest4
MVP
MPC
0.62
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at