NM_021937.5:c.130G>C

Variant names:

• chr3-128153637-G-C
• rs934315994
• NM_021937.5:c.130G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021937.5(EEFSEC):​c.130G>C​(p.Glu44Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,598,158 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 0.000020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: EEFSEC NM_021937.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.55
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4161063).

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.130G>C	p.Glu44Gln	missense	Exon 1 of 7	NP_068756.2	P57772-1
	RUVBL1	NM_001319086.1		c.-474C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001306015.1	E7ETR0
	EEFSEC	NM_001437809.1		c.130G>C	p.Glu44Gln	missense	Exon 1 of 8	NP_001424738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	ENST00000254730.11	TSL:1 MANE Select	c.130G>C	p.Glu44Gln	missense	Exon 1 of 7	ENSP00000254730.5	P57772-1
	RUVBL1	ENST00000464873.5	TSL:2	c.-474C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000420738.1	E7ETR0
	EEFSEC	ENST00000868107.1		c.130G>C	p.Glu44Gln	missense	Exon 1 of 8	ENSP00000538166.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152120 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000724

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1446038 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 719730

African (AFR) AF: 0.0000621 AC: 2 AN: 32202

American (AMR) AF: 0.00 AC: 0 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39204

South Asian (SAS) AF: 0.00 AC: 0 AN: 85464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5526

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109910

Other (OTH) AF: 0.0000167 AC: 1 AN: 59986

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152120 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.0000724 AC: 3 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

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	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Benign	0.11	T
Sift4G	Benign	0.22	T
Polyphen		0.85	P
Vest4		0.10
MutPred		0.69		Loss of stability (P = 0.1269)
MVP		0.64
MPC		1.2
ClinPred		0.98	D
GERP RS		4.3
PromoterAI		0.026	Neutral
Varity_R		0.64
gMVP		0.75
Mutation Taster		=261/39	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: rs934315994; hg19: chr3-127872480;