NM_183381.3:c.52A>G

Variant names:

• chr3-149846078-A-G
• rs760934570
• NM_183381.3:c.52A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_183381.3(RNF13):​c.52A>G​(p.Ile18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: RNF13 NM_183381.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.56
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12352997).
• BP6: Variant 3-149846078-A-G is Benign according to our data. Variant chr3-149846078-A-G is described in ClinVar as Benign. ClinVar VariationId is 1421910.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 6 AD gene.

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.52A>G	p.Ile18Val	missense	Exon 2 of 10	NP_899237.1	O43567-1
	RNF13	NM_001378285.1		c.52A>G	p.Ile18Val	missense	Exon 3 of 11	NP_001365214.1	O43567-1
	RNF13	NM_001378286.1		c.52A>G	p.Ile18Val	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.52A>G	p.Ile18Val	missense	Exon 2 of 10	ENSP00000376628.3	O43567-1
	RNF13	ENST00000344229.7	TSL:1	c.52A>G	p.Ile18Val	missense	Exon 3 of 11	ENSP00000341361.3	O43567-1
	RNF13	ENST00000910573.1		c.52A>G	p.Ile18Val	missense	Exon 2 of 11	ENSP00000580632.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251238 AF XY: 0.0000516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000308 AC: 45 AN: 1460732 Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 22 AN XY: 726678

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4982

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111880

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68022

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

Alfa AF: 0.000100 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

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	Benign	0.068
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.053
Sift	Benign	0.42	T
Sift4G	Benign	0.62	T
Polyphen		0.0010	B
Vest4		0.32
MutPred		0.33		Gain of sheet (P = 0.0827)
MVP		0.43
MPC		0.15
ClinPred		0.33	T
GERP RS		1.6
PromoterAI		-0.059	Neutral
Varity_R		0.048
gMVP		0.48
Mutation Taster		=79/21	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: rs760934570; hg19: chr3-149563865;