Variant 3-128153688-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021937.5(EEFSEC):c.181C>T(p.Pro61Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000377 in 1,592,282 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

EEFSEC
NM_021937.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEFSEC	NM_021937.5 linkuse as main transcript	c.181C>T	p.Pro61Ser	missense_variant	1/7	ENST00000254730.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEFSEC	ENST00000254730.11 linkuse as main transcript	c.181C>T	p.Pro61Ser	missense_variant	1/7	1	NM_021937.5	P1	P57772-1
EEFSEC	ENST00000483457.1 linkuse as main transcript	c.181C>T	p.Pro61Ser	missense_variant	1/5	5
RUVBL1	ENST00000464873.5 linkuse as main transcript	c.-525G>A		5_prime_UTR_variant	1/10	2
EEFSEC	ENST00000484438.1 linkuse as main transcript	n.21C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000142

AC:

AN:

211358

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

117826

show subpopulations

Gnomad AFR exome

AF:

0.0000867

Gnomad AMR exome

AF:

0.000511

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000844

Gnomad OTH exome

AF:

0.000556

GnomAD4 exome

AF:

0.0000354

AC:

AN:

1440014

Hom.:

Cov.:

AF XY:

0.0000335

AC XY:

AN XY:

716490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000589

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:

0.0000162

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000110

AC:

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

May 28, 2024

The c.181C>T (p.P61S) 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 181, causing the proline (P) at amino acid position 61 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.77

M_CAP

Pathogenic

0.50

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Uncertain

-0.081

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.6

D;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;P

Vest4

0.59

MutPred

0.32

Gain of phosphorylation at P61 (P = 0.0391);Gain of phosphorylation at P61 (P = 0.0391);

MVP

0.78

MPC

1.7

ClinPred

0.19

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.91

gMVP

0.82

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