NM_021937.5:c.187C>T

Variant names:

• chr3-128153694-C-T
• rs1003961919
• NM_021937.5:c.187C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3290283).

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.187C>T	p.Arg63Cys	missense	Exon 1 of 7	NP_068756.2	P57772-1
	EEFSEC	NM_001437809.1		c.187C>T	p.Arg63Cys	missense	Exon 1 of 8	NP_001424738.1
	EEFSEC	NM_001437810.1		c.187C>T	p.Arg63Cys	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.187C>T	p.Arg63Cys	missense	Exon 1 of 7	ENSP00000254730.5	P57772-1
	EEFSEC	ENST00000868107.1		c.187C>T	p.Arg63Cys	missense	Exon 1 of 8	ENSP00000538166.1
	EEFSEC	ENST00000868109.1		c.187C>T	p.Arg63Cys	missense	Exon 1 of 8	ENSP00000538168.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152128 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.00000487 AC: 1 AN: 205362 AF XY: 0.00000872

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000305

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437176 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 714858

African (AFR) AF: 0.00 AC: 0 AN: 32186

American (AMR) AF: 0.0000455 AC: 2 AN: 43964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 38952

South Asian (SAS) AF: 0.00 AC: 0 AN: 84242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107598

Other (OTH) AF: 0.00 AC: 0 AN: 59748

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152128 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.000393 AC: 6 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000338 Hom.: 0

Bravo AF: 0.000117

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	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.51	N
PhyloP100		5.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.48		Gain of catalytic residue at L64 (P = 0.0155)
MVP		0.72
MPC		2.0
ClinPred		0.73	D
GERP RS		2.7
PromoterAI		-0.057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.45
gMVP		0.50
Mutation Taster		=60/40	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: rs1003961919; hg19: chr3-127872537;