chr3-149872041-A-G

Position:

• chr3-149872041-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_183381.3(RNF13):​c.208A>G​(p.Asn70Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,436,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RNF13 NM_183381.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2822601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF13	NM_183381.3	c.208A>G	p.Asn70Asp	missense_variant	4/10	ENST00000392894.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF13	ENST00000392894.8	c.208A>G	p.Asn70Asp	missense_variant	4/10	1	NM_183381.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436096 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 714064

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: 0.00

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0041	T;T;.;T;.;.;T;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	.;T;T;D;T;T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.28	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;L;.;.;.;.;.;.
MutationTaster	Benign	0.62	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.060	N;N;N;N;N;N;N;N
REVEL	Benign	0.060
Sift	Benign	0.61	T;T;T;T;T;T;T;T
Sift4G	Benign	0.61	T;T;T;T;T;T;T;T
Polyphen		0.13	B;B;.;.;.;.;.;.
Vest4		0.59
MutPred		0.42		Gain of catalytic residue at N70 (P = 0.0868);Gain of catalytic residue at N70 (P = 0.0868);Gain of catalytic residue at N70 (P = 0.0868);Gain of catalytic residue at N70 (P = 0.0868);Gain of catalytic residue at N70 (P = 0.0868);Gain of catalytic residue at N70 (P = 0.0868);Gain of catalytic residue at N70 (P = 0.0868);Gain of catalytic residue at N70 (P = 0.0868);
MVP		0.58
MPC		0.23
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs1712130287; hg19: chr3-149589828;