3-128341257-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_021937.5(EEFSEC):​c.811C>A​(p.Gln271Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,611,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

EEFSEC
NM_021937.5 missense

Scores

10
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90
Variant links:
Genes affected
EEFSEC (HGNC:24614): (eukaryotic elongation factor, selenocysteine-tRNA specific) Predicted to enable translation elongation factor activity. Predicted to be involved in selenocysteine incorporation. Predicted to be located in cytoplasm and nucleus. Predicted to be part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EEFSECNM_021937.5 linkuse as main transcriptc.811C>A p.Gln271Lys missense_variant 5/7 ENST00000254730.11 NP_068756.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EEFSECENST00000254730.11 linkuse as main transcriptc.811C>A p.Gln271Lys missense_variant 5/71 NM_021937.5 ENSP00000254730 P1P57772-1
EEFSECENST00000483457.1 linkuse as main transcriptc.646C>A p.Gln216Lys missense_variant 4/55 ENSP00000417660
EEFSECENST00000483569.1 linkuse as main transcriptn.214C>A non_coding_transcript_exon_variant 2/25
EEFSECENST00000484438.1 linkuse as main transcriptn.389C>A non_coding_transcript_exon_variant 3/33

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000201
AC:
5
AN:
248510
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134202
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000446
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1459276
Hom.:
0
Cov.:
32
AF XY:
0.0000262
AC XY:
19
AN XY:
725806
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000405
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152222
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000414
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingAmbry GeneticsSep 07, 2022The c.811C>A (p.Q271K) alteration is located in exon 5 (coding exon 5) of the EEFSEC gene. This alteration results from a C to A substitution at nucleotide position 811, causing the glutamine (Q) at amino acid position 271 to be replaced by a lysine (K). 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
Pathogenic
0.94
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Pathogenic
0.24
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.51
D;T
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
1.0
D
M_CAP
Uncertain
0.090
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Uncertain
0.39
D
MutationAssessor
Pathogenic
3.9
H;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Uncertain
0.60
Sift
Pathogenic
0.0
D;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.85
MVP
0.85
MPC
0.55
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.92
gMVP
0.71

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.

Other links and lift over

dbSNP: rs750034735; hg19: chr3-128060100; API