chr3-128153637-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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 rank	MANE	Protein	UniProt
EEFSEC	NM_021937.5	c.130G>A	p.Glu44Lys	missense_variant	Exon 1 of 7	ENST00000254730.11	NP_068756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEFSEC	ENST00000254730.11	c.130G>A	p.Glu44Lys	missense_variant	Exon 1 of 7	1	NM_021937.5	ENSP00000254730.5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.028	D;T
Polyphen		0.96	D;P
Vest4		0.27
MutPred		0.74		Gain of methylation at E44 (P = 0.0315);Gain of methylation at E44 (P = 0.0315);
MVP		0.62
MPC		1.3
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.84
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-127872480;