Variant 3-128153694-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021937.5(EEFSEC):c.187C>T(p.Arg63Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000503 in 1,589,304 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 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EEFSEC
NM_021937.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

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]

EEFSEC links:

RUVBL1 (HGNC:10474): (RuvB like AAA ATPase 1) This gene encodes a protein that has both DNA-dependent ATPase and DNA helicase activities and belongs to the ATPases associated with diverse cellular activities (AAA+) protein family. The encoded protein associates with several multisubunit transcriptional complexes and with protein complexes involved in both ATP-dependent remodeling and histone modification. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

RUVBL1 links:

Genome browser will be placed here

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=0.3290283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEFSEC	NM_021937.5 linkuse as main transcript	c.187C>T	p.Arg63Cys	missense_variant	1/7	ENST00000254730.11	NP_068756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEFSEC	ENST00000254730.11 linkuse as main transcript	c.187C>T	p.Arg63Cys	missense_variant	1/7	1	NM_021937.5	ENSP00000254730	P1	P57772-1
EEFSEC	ENST00000483457.1 linkuse as main transcript	c.187C>T	p.Arg63Cys	missense_variant	1/5	5		ENSP00000417660
RUVBL1	ENST00000464873.5 linkuse as main transcript	c.-531G>A		5_prime_UTR_variant	1/10	2		ENSP00000420738
EEFSEC	ENST00000484438.1 linkuse as main transcript	n.27C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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

AF:

0.00000139

AC:

AN:

1437176

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714858

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000455

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000393

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

Alfa

AF:

0.0000338

Hom.:

Bravo

AF:

0.000117

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

Nov 18, 2023

The c.187C>T (p.R63C) alteration is located in exon 1 (coding exon 1) of the EEFSEC gene. This alteration results from a C to T substitution at nucleotide position 187, causing the arginine (R) at amino acid position 63 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.77

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.51

N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.19

MutPred

0.48

Gain of catalytic residue at L64 (P = 0.0155);Gain of catalytic residue at L64 (P = 0.0155);

MVP

0.72

MPC

2.0

ClinPred

0.73

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.45

gMVP

0.50

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