17-80353558-G-C

Variant names:

• chr17-80353558-G-C
• NM_001256071.3:c.10470G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256071.3(RNF213):​c.10470G>C​(p.Glu3490Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,356 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. Synonymous variant affecting the same amino acid position (i.e. E3490E) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13570961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF213	NM_001256071.3	c.10470G>C	p.Glu3490Asp	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.10470G>C	p.Glu3490Asp	missense_variant	Exon 34 of 68	1	NM_001256071.3	ENSP00000464087.1
RNF213	ENST00000508628.6	c.10617G>C	p.Glu3539Asp	missense_variant	Exon 35 of 69	5		ENSP00000425956.2
RNF213-AS1	ENST00000575034.5	n.1921C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
RNF213-AS1	ENST00000613190.1	n.254C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461356 Hom.: 0 Cov.: 55 AF XY: 0.00000138 AC XY: 1 AN XY: 726938

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.29
DANN	Benign	0.69
DEOGEN2	Benign	0.037	T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.20
Sift	Uncertain	0.024	D;.
Sift4G	Benign	0.13	T;T
Vest4		0.16
MVP		0.34
MPC		0.38
ClinPred		0.47	T
GERP RS		-5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78327358;