NM_006666.3:c.411C>G

Variant names:

• chr19-49007317-C-G
• NM_006666.3:c.411C>G

Variant summary

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

The NM_006666.3(RUVBL2):​c.411C>G​(p.Ile137Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RUVBL2 NM_006666.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02
• Publications: 0 publications found

Genes affected

RUVBL2 (HGNC:10475): (RuvB like AAA ATPase 2) This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helicase essential for homologous recombination and DNA double-strand break repair. Functional analysis showed that this gene product has both ATPase and DNA helicase activities. This gene is physically linked to the CGB/LHB gene cluster on chromosome 19q13.3, and is very close (55 nt) to the LHB gene, in the opposite orientation. [provided by RefSeq, Jul 2008]

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_006666.3. 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
	RUVBL2	NM_006666.3	MANE Select	c.411C>G	p.Ile137Met	missense	Exon 6 of 15	NP_006657.1	Q9Y230-1
	RUVBL2	NM_001321190.2		c.309C>G	p.Ile103Met	missense	Exon 6 of 15	NP_001308119.1	B3KNL2
	RUVBL2	NM_001321191.1		c.276C>G	p.Ile92Met	missense	Exon 6 of 15	NP_001308120.1	Q9Y230-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL2	ENST00000595090.6	TSL:1 MANE Select	c.411C>G	p.Ile137Met	missense	Exon 6 of 15	ENSP00000473172.1	Q9Y230-1
	RUVBL2	ENST00000221413.10	TSL:1	n.411C>G		non_coding_transcript_exon	Exon 6 of 15	ENSP00000221413.6	X6R2L4
	RUVBL2	ENST00000888169.1		c.432C>G	p.Ile144Met	missense	Exon 6 of 15	ENSP00000558228.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.30
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.0
PrimateAI	Pathogenic	0.81	D
Sift4G	Uncertain	0.024	D
Polyphen		0.049	B
Vest4		0.74
MutPred		0.69		Gain of sheet (P = 0.0149)
MVP		0.40
MPC		1.2
ClinPred		0.69	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.90
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

hg19: chr19-49510574;