17-80353530-C-T

Variant names:

• chr17-80353530-C-T
• rs144139703
• NM_001256071.3:c.10442C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001256071.3(RNF213):​c.10442C>T​(p.Ala3481Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,611,498 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A3481A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.143
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074279904).
• BP6: Variant 17-80353530-C-T is Benign according to our data. Variant chr17-80353530-C-T is described in ClinVar as Benign. ClinVar VariationId is 723852.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00121 (184/152196) while in subpopulation AFR AF = 0.00417 (173/41496). AF 95% confidence interval is 0.00366. There are 1 homozygotes in GnomAd4. There are 82 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256071.3. 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
	RNF213	NM_001256071.3	MANE Select	c.10442C>T	p.Ala3481Val	missense	Exon 34 of 68	NP_001243000.2	A0A0A0MTR7
	RNF213	NM_001410195.1		c.10589C>T	p.Ala3530Val	missense	Exon 35 of 69	NP_001397124.1	A0A0A0MTC1
	RNF213	NM_020914.5		c.10589C>T	p.Ala3530Val	missense	Exon 35 of 69	NP_065965.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	ENST00000582970.6	TSL:1 MANE Select	c.10442C>T	p.Ala3481Val	missense	Exon 34 of 68	ENSP00000464087.1	A0A0A0MTR7
	RNF213	ENST00000508628.6	TSL:5	c.10589C>T	p.Ala3530Val	missense	Exon 35 of 69	ENSP00000425956.2	A0A0A0MTC1
	RNF213-AS1	ENST00000575034.5	TSL:2	n.1949G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 152078 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00418

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000275 AC: 67 AN: 243696 AF XY: 0.000258

Gnomad AFR exome AF: 0.00409

Gnomad AMR exome AF: 0.0000593

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000918

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000135 AC: 197 AN: 1459302 Hom.: 0 Cov.: 30 AF XY: 0.000113 AC XY: 82 AN XY: 725638

African (AFR) AF: 0.00472 AC: 158 AN: 33454

American (AMR) AF: 0.0000906 AC: 4 AN: 44136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1110786

Other (OTH) AF: 0.000298 AC: 18 AN: 60324

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152196 Hom.: 1 Cov.: 33 AF XY: 0.00110 AC XY: 82 AN XY: 74396

African (AFR) AF: 0.00417 AC: 173 AN: 41496

American (AMR) AF: 0.000523 AC: 8 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000476 Hom.: 0

Bravo AF: 0.00139

ESP6500AA AF: 0.00454 AC: 20

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000346 AC: 42

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	0.085
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.2
DANN	Benign	0.67
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.14
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.048
Sift	Benign	0.31	T
Sift4G	Benign	0.080	T
Vest4		0.062
MVP		0.030
MPC		0.34
ClinPred		0.0079	T
GERP RS		0.79
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Mutation Taster		=99/1	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: rs144139703; hg19: chr17-78327330;