rs934315994

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-128153637-G-A
• chr3-128153637-G-C

Variant summary

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

The NM_001319086.1(RUVBL1):​c.-474C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,446,038 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RUVBL1 NM_001319086.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319086.1. 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>A	p.Glu44Lys	missense	Exon 1 of 7	NP_068756.2	P57772-1
	RUVBL1	NM_001319086.1		c.-474C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001306015.1	E7ETR0
	EEFSEC	NM_001437809.1		c.130G>A	p.Glu44Lys	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>A	p.Glu44Lys	missense	Exon 1 of 7	ENSP00000254730.5	P57772-1
	RUVBL1	ENST00000464873.5	TSL:2	c.-474C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000420738.1	E7ETR0
	EEFSEC	ENST00000868107.1		c.130G>A	p.Glu44Lys	missense	Exon 1 of 8	ENSP00000538166.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446038 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719730

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 59986

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.5	L
PhyloP100		8.6
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.28
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.028	D
Polyphen		0.96	D
Vest4		0.27
MutPred		0.74		Gain of methylation at E44 (P = 0.0315)
MVP		0.62
MPC		1.3
ClinPred		0.98	D
GERP RS		4.3
PromoterAI		0.014	Neutral
Varity_R		0.84
gMVP		0.82
Mutation Taster		=55/45	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;