NM_001256071.3:c.10487C>T

Variant names:

• chr17-80353575-C-T
• rs139113160
• NM_001256071.3:c.10487C>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.10487C>T​(p.Ser3496Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,613,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00090 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.677
• 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=0.009649754).
• BP6: Variant 17-80353575-C-T is Benign according to our data. Variant chr17-80353575-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 726381.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0009 (137/152242) while in subpopulation AFR AF = 0.00306 (127/41538). AF 95% confidence interval is 0.00263. There are 0 homozygotes in GnomAd4. There are 58 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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.10487C>T	p.Ser3496Leu	missense	Exon 34 of 68	NP_001243000.2	A0A0A0MTR7
	RNF213	NM_001410195.1		c.10634C>T	p.Ser3545Leu	missense	Exon 35 of 69	NP_001397124.1	A0A0A0MTC1
	RNF213	NM_020914.5		c.10634C>T	p.Ser3545Leu	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.10487C>T	p.Ser3496Leu	missense	Exon 34 of 68	ENSP00000464087.1	A0A0A0MTR7
	RNF213	ENST00000508628.6	TSL:5	c.10634C>T	p.Ser3545Leu	missense	Exon 35 of 69	ENSP00000425956.2	A0A0A0MTC1
	RNF213-AS1	ENST00000575034.5	TSL:2	n.1904G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000901 AC: 137 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000260 AC: 65 AN: 249616 AF XY: 0.000222

Gnomad AFR exome AF: 0.00290

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000446

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000172 AC: 251 AN: 1461696 Hom.: 1 Cov.: 34 AF XY: 0.000164 AC XY: 119 AN XY: 727142

African (AFR) AF: 0.00361 AC: 121 AN: 33474

American (AMR) AF: 0.000492 AC: 22 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000782 AC: 87 AN: 1111876

Other (OTH) AF: 0.000331 AC: 20 AN: 60390

GnomAD4 genome AF: 0.000900 AC: 137 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74442

African (AFR) AF: 0.00306 AC: 127 AN: 41538

American (AMR) AF: 0.000458 AC: 7 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000467 Hom.: 0

Bravo AF: 0.00119

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000313 AC: 38

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely 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	0.10
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.6
DANN	Benign	0.50
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.68
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.079
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.016	D
Vest4		0.066
MVP		0.30
MPC		0.30
ClinPred		0.055	T
GERP RS		1.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Mutation Taster		=89/11	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: rs139113160; hg19: chr17-78327375;