17-80353551-C-G

Variant names:

• chr17-80353551-C-G
• rs369786853
• NM_001256071.3:c.10463C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001256071.3(RNF213):​c.10463C>G​(p.Ala3488Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

Genes affected

RNF213 (HGNC:14539): (ring finger protein 213) This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

RNF213-AS1 (HGNC:54402): (RNF213 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0446167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF213	NM_001256071.3	c.10463C>G	p.Ala3488Gly	missense_variant	Exon 34 of 68	ENST00000582970.6	NP_001243000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF213	ENST00000582970.6	c.10463C>G	p.Ala3488Gly	missense_variant	Exon 34 of 68	1	NM_001256071.3	ENSP00000464087.1
RNF213	ENST00000508628.6	c.10610C>G	p.Ala3537Gly	missense_variant	Exon 35 of 69	5		ENSP00000425956.2
RNF213-AS1	ENST00000575034.5	n.1928G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2
RNF213-AS1	ENST00000613190.1	n.261G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461406 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726966

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.090
DANN	Benign	0.66
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.061
Sift	Benign	0.46	T;.
Sift4G	Benign	0.39	T;T
Vest4		0.078
MVP		0.040
MPC		0.52
ClinPred		0.14	T
GERP RS		-8.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369786853; hg19: chr17-78327351;