3-128153621-G-T

Variant names:

• chr3-128153621-G-T
• rs1164834792
• NM_021937.5:c.114G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021937.5(EEFSEC):​c.114G>T​(p.Lys38Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000554 in 1,444,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K38R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: EEFSEC NM_021937.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021937.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	NM_021937.5	MANE Select	c.114G>T	p.Lys38Asn	missense	Exon 1 of 7	NP_068756.2	P57772-1
	EEFSEC	NM_001437809.1		c.114G>T	p.Lys38Asn	missense	Exon 1 of 8	NP_001424738.1
	EEFSEC	NM_001437810.1		c.114G>T	p.Lys38Asn	missense	Exon 1 of 7	NP_001424739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	ENST00000254730.11	TSL:1 MANE Select	c.114G>T	p.Lys38Asn	missense	Exon 1 of 7	ENSP00000254730.5	P57772-1
	EEFSEC	ENST00000868107.1		c.114G>T	p.Lys38Asn	missense	Exon 1 of 8	ENSP00000538166.1
	EEFSEC	ENST00000868109.1		c.114G>T	p.Lys38Asn	missense	Exon 1 of 8	ENSP00000538168.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000554 AC: 8 AN: 1444740 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718988

African (AFR) AF: 0.00 AC: 0 AN: 31978

American (AMR) AF: 0.00 AC: 0 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.000231 AC: 6 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39024

South Asian (SAS) AF: 0.00 AC: 0 AN: 85230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5400

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109406

Other (OTH) AF: 0.00 AC: 0 AN: 59916

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.74	D
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.099
MutPred		0.56		Loss of ubiquitination at K38 (P = 0.0043)
MVP		0.72
MPC		2.0
ClinPred		1.0	D
GERP RS		3.4
PromoterAI		0.031	Neutral
Varity_R		0.86
gMVP		0.75
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

dbSNP: rs1164834792; hg19: chr3-127872464;