chr3-149846042-G-A

Variant names:

• chr3-149846042-G-A
• rs1722610564
• NM_183381.3:c.16G>A

Variant summary

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

The NM_183381.3(RNF13):​c.16G>A​(p.Gly6Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF13 NM_183381.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.01
• Publications: 0 publications found

Genes affected

RNF13 (HGNC:10057): (ring finger protein 13) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. The specific function of this gene has not yet been determined. Alternatively spliced transcript variants that encode the same protein have been reported. A pseudogene, which is also located on chromosome 3, has been defined for this gene. [provided by RefSeq, Jul 2008]

ANKUB1 (HGNC:29642): (ankyrin repeat and ubiquitin domain containing 1)

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_183381.3. 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
	RNF13	NM_183381.3	MANE Select	c.16G>A	p.Gly6Arg	missense	Exon 2 of 10	NP_899237.1	O43567-1
	RNF13	NM_001378285.1		c.16G>A	p.Gly6Arg	missense	Exon 3 of 11	NP_001365214.1	O43567-1
	RNF13	NM_001378286.1		c.16G>A	p.Gly6Arg	missense	Exon 2 of 10	NP_001365215.1	O43567-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF13	ENST00000392894.8	TSL:1 MANE Select	c.16G>A	p.Gly6Arg	missense	Exon 2 of 10	ENSP00000376628.3	O43567-1
	RNF13	ENST00000344229.7	TSL:1	c.16G>A	p.Gly6Arg	missense	Exon 3 of 11	ENSP00000341361.3	O43567-1
	RNF13	ENST00000910573.1		c.16G>A	p.Gly6Arg	missense	Exon 2 of 11	ENSP00000580632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		9.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.022	D
Polyphen		0.97	D
Vest4		0.86
MutPred		0.52		Loss of sheet (P = 0.0126)
MVP		0.72
MPC		0.77
ClinPred		0.84	D
GERP RS		5.6
PromoterAI		-0.013	Neutral
Varity_R		0.46
gMVP		0.81
Mutation Taster		=15/85	disease causing

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: rs1722610564; hg19: chr3-149563829;